_____________________________________________________________________________________________________ *Corresponding author: E-mail: pkorisadiran@pgschool.lautech.edu.ng; Asian Journal of Immunology 3(1): 11-22, 2020; Article no.AJI.53370 Effects of D-Ribose-L-Cysteine on Lipid Profile, Atherogenic Index and Infertility in Streptozotocin- Induced Male Diabetic Wistar Rats Abiodun Oluwabusola Adedeji1,2 and Patrick Kunle Orisadiran3* 1 Department of Anatomy, Olabisi Onabanjo University, Ago Iwoye, Nigeria. 2Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Nigeria. 3Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria. Authors’ contributions This work was carried out in collaboration between both authors. Author AOA participated in study design, data collection and interpretation, contributed to drafting/ revising of manuscript. Author PKO participated in study design, data analysis and interpretation, did literature search and drafted/edited/ revised manuscript. Both authors read and approved the final manuscript. Article Information Editor(s): (1) Dr. Jaffu Othniel Chilongola, Department of Biochemistry and Molecular Biology, Kilimanjaro Christian Medical University College, Tumaini University, Tanzania. Reviewers: (1) Rupali Sengupta, India. (2) Ann Nkeiruka, National Root Crops Research Institute, Nigeria. Complete Peer review History: http://www.sdiarticle4.com/review-history/53370 Received 02 November 2019 Accepted 07 January 2020 Published 20 January 2020 ABSTRACT Aims: The present study aimed at determining the effects of D-Ribose-L-Cysteine on lipid profile, atherogenic index, and infertility in streptozotocin-induced diabetic male Wistar rats. Methods: A total of twenty-eight adult male Wistar rats were divided into four groups of seven rats each. 1: Normal control group, 2: Diabetic control group, 3: Normal rats treated with 30 mg/kg body weight of D-Ribose-L-cysteine, 4: Diabetic rats treated with 30 mg/kg body weight of D-Ribose-L- cysteine. Group 2 and 4 were injected intraperitoneally with a single dose of streptozotocin (STZ) (65 mg/kg in 0.1 M cold citrate buffer, pH 7.5) prior to D-Ribose-L-cysteine treatment. Group 4 were subsequently administered D-Ribose-L-cysteine orally 72 hours post administration of streptozotocin, twice daily for 28 days. Parameters tested include: fasting blood and serum glucose, malondialdehyde (MDA) concentration, sperm motility, morphology and count. Testosterone (TT), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were also examined. Original Research Article Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 12 Results: The results showed that diabetic rats showed weights loss, increased MDA, increase blood and serum glucose levels, elevated lipid profile, altered TT, FSH and LH as well as reduced sperm count, motility and morphology. These effects were ameliorated in diabetic rats treated with D-Ribose-L-cysteine. Conclusion: Current study revealed that D-Ribose-L-Cysteine attenuates the oxidative stress in streptozotocin-induced diabetic rats on blood glucose, lipid profile, reproductive hormone and sperm parameters. Keywords: D-Ribose and L-Cysteine; wistar rats; diabetic rat; sperm; hormone; streptozotocin. 1. INTRODUCTION Diabetes mellitus is a group of metabolic disorders resulting from a deficiency in insulin secretions and/or actions [1]. This deficiency, in turn, leads to accumulation of glucose in the bloodstream with obstruction of carbohydrate, fat and protein metabolism. Disease progression results in tissue damage leading to severe diabetic complications such as impairment or loss of vision, impairment of kidney function, cardiovascular and microbial complications [2]. The world prevalence of diabetes among adults between 20 and 79 years was estimated to be 6.4%, affecting 285 million adults, in 2010, and will increase to 7.7% and 439 million adults by 2030 [3]. Out of the two types of diabetes (insulin dependent and non-insulin dependent), the incidence of non-insulin dependent diabetes mellitus is much higher than the insulin- dependent diabetes mellitus [4]. Glucose is the main oxidizable substrate in various cell types. Homeostasis is maintained in a diabetic state by the activation of catabolic pathways such as gluconeogenesis and glycogenolysis [5]. As a result, lipolysis is also increased, which trigger dyslipidemia, a risk factor for the development of atherosclerosis that affects 97 percent of diabetic patients [6,7]. Dyslipidemia is characterized by elevated levels of triacylglycerol plasma and total cholesterol, increasing the concentration of very low-density lipoproteins (VLDL-cholesterol) and low-density lipoproteins (LDL-cholesterol) and decreasing the concentration of high-density lipoproteins (HDL- cholesterol) [7,8]. In different studies by Valko et al. [9] and Schilling [10], they showed that an increase in LDL-cholesterol that occurs due to the release of oxidizing agents during the metabolic pathways activated by hyperglycemia is directly related to the development of atherosclerosis, the inflammatory process triggered by the oxidation of LDL-cholesterol. Oxidized LDLs are phagocytosed by macrophages in the subendothelial layer, thereby transforming into foam cells that contribute to the formation of atherosclerotic plaque and, consequently, atherosclerosis [6,11]. Reproductive disorders in diabetic males have been widely studied. Experimental studies by O’Neill et al. [12] and Ricci et al. [13] revealed different structural and physiological reproductive dysfunctions in cases of diabetes in males. Diabetes mellitus affects male reproductive functions at multiple levels as well as its negative effects on endocrine control of spermatogenesis and/or by impairing erection and ejaculation [14]. Ricci et al. [13] established that insulin- dependent diabetes is accompanied by reduced semen volume and decreased sperm motility and vitality. This corroborates with the report of Agbaje et al. [15] which stated that a high level of blood sugar in the bloodstream may affect sperm quality and consequently decreases male fertility potentials. Also, Joao and co. [16] confirmed high rates of infertility and poor reproductive outcomes in diabetic men compared with healthy men. Therefore, effective control of the blood glucose level is crucial in preventing, controlling or reversing diabetic complications associated with diabetics, thus improving the quality of life in diabetic patients [17]. A study has shown that antioxidant substances can reduce chronic degenerative diseases such as diabetes mellitus and its complications [18]. Antioxidants are stable substances that act as reducing agents capable of reducing oxidized substances and making them stable, thus repairing the structure of the cellular macromolecules [19]. D-ribose is an antioxidant and a prodrug form of L-cysteine known to aid the elevation of intracellular levels of glutathione (GSH) [20]. GSH is a coenzyme that mediates the protection against free radicals generated during the Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 13 oxidative metabolism of acetaminophen by the hepatic cytochrome P-450 system [21]. Whole glutathione consumption cannot be effective because it would be destroyed in the digestion process before reaching the cell. The ribose component of the D-Ribose-L-Cysteine solves these challenges allowing the cells to produce glutathione when needed by effectively protecting and delivering the fragile cysteine molecule [22]. In view of the discussed above, this study aimed to determine the beneficial effects of D-Ribose-L- Cysteine on lipid profile, atherogenic index, and infertility in streptozotocin-induced diabetic male Wistar rats. 2. MATERIALS AND METHODS 2.1 Chemicals Streptozotocin (STZ) was a product of Sigma Chemical Company St. Louis U.S.A. All assay kits were from Randox Laboratories Limited UK. Chemicals and reagents used were of analytical grade. D-Ribose-L-Cysteine supplement was obtained from Max International, Salt Lake City, Utah, USA. 2.2 Experimental Design A total of 28 Albino rats of Wistar strain, with an average weight of 160 g were obtained from the Animal House of Physiology Department, Ladoke Akintola University of Technology, Nigeria. The animals were divided into 4 groups of 7 rats each and housed in separate cages in the same environment. The animals were allowed to acclimatize in the laboratory for two weeks before the commencement of the experiments. 2.3 Diabetes Induction Streptozotocin (65 mg/kg in 0.1 M cold citrate buffer, pH 7.5) was administered to Wistar rats fasted overnight by interperitoneally injection of freshly prepared solution. The animals were considered as diabetic if the blood glucose values of the overnight fasted rats, were > 250 mg/dl on the third day. Group 1: Control rats given citrate buffer only (0.01 M, pH 7.5), Group 2: Diabetic control (untreated rats) Group 3: Rats treated with 30 mg/kg body weight of D-Ribose-L-cysteine. Group 4: Diabetic rats treated with 30 mg/kg body weight of D-Ribose-L-cysteine The diabetic rats were then kept for 24 hours on 5% glucose solution bottles in their cages to prevent hypoglycemia. Blood was collected every 3 days through the rat’s tail vein for glucose estimation using One Touch Glucometer; After 28 days of treatment, the body weight and fasting blood glucose, serum glucose of the animals were again determined. 2.4 Collection of Blood The rats were fasted overnight after 28 day, anaesthetized with chloroform and sacrificed. Blood was collected by cardiac puncture into plain sample bottles, allowed to coagulate and then centrifuged at 3000 rpm for 15 minutes to obtain serum. The serum was kept under refrigeration at 4ºC for biochemical examination. 2.5 Biochemical Examination Serum total cholesterol was determined using the method of Zak [23], plasma triglyceride estimated by the method of Mendez et al. [24], HDL-C by Lopez- Vitrella et al. [25], LDL-C and VLDL triglyceride values were calculated by the modified method of Friedewald formula [26]. Serum MDA was measured by a thiobarbituric acid assay procedure [27]. 2.6 Semen Analysis The caudal epididymis of the rats was incised and a drop of epididymal fluid was smeared onto a glass slide, covered by a 22 · 22 mm. The slide was examined under the light microscope at 100 magnification to evaluate different fields [28]. After assessing different microscopic fields, the relative percentage of motile sperm was estimated and reported to the nearest 5% using the subjective determination of motility [29]. The sperm count was determined using the Neubauer improved hemocytometer. The epididymal fluid ratio of 1:20 was prepared by adding 0.1 ml of fluid to 1.9 ml of water. The dilution was mixed thoroughly and both sides of the counting chamber were scored and the average was taken. Spermatozoa within five of the red blood cell squares including those which lie across the outermost lines at the top and right sides were counted, while those at the bottom and left sides were left out. The number of spermatozoa counted was expressed in millions/ml [30]. Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 14 2.7 Reproductive Hormones The serum levels of testosterone, luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) were measured using enzyme-linked immunoassay kit (Abcam) according to the manufacturer’s instructions. 2.8 Statistical Analysis Results were presented as Mean ± SD. Paired Student’s t-test was used to compare variations amongst groups. The minimum level of significance was considered at p˂0.05. Statistical analysis was carried out using a software program (GraphPad Prism Ver. 5; GraphPad Software, San Diego, CA). 3. RESULTS 3.1 Effect of D-Ribose-L-Cysteine on Bodyweight and Serum Glucose on STZ Induced Diabetic Rats There was a significant increased (p<0.05) in the bodyweight of normal control and D-Ribose-L- Cysteine treated group whereas the body weight of diabetic rats significantly reduced during the period of the experiment (Fig. 1). The blood glucose levels increased significantly (p < 0.05) after the induction of diabetes but after the administration of D-Ribose-L-Cysteine the blood glucose levels also decreased significantly (p < 0.05) compared to the diabetic control (Fig. 2a). The serum glucose level in the diabetic control group (15.5±1.3 mmol/L) was significantly (P<0.05) higher compared to normal control group (6.4±1.3 mmol/L), while treated diabetic rats showed a slight significant decreased (P<0.05) in the serum glucose (9.7±1.2 mmol/L) compared to the diabetic control rats (Fig. 2b). 3.2 Effect of D-Ribose-L-Cysteine on Lipid Peroxidation in STZ Induced Diabetic Rats Figure 3 shows the changes in serum MDA concentration. The mean value of serum MDA levels in the diabetic rats (7.77±0.78 nmol/ml) significantly increased (p<0.05) when compared with the normal control (5.7±0.90 nmol/ml) but significantly decreased (p<0.05) in diabetic rats treated with D-Ribose-L-Cysteine (5.93±0.89 nmol/ml). 3.3 Effect of D-Ribose-L-Cysteine on Lipid Profile in STZ Induced Diabetic Rats Serum levels of normal and diabetic rats treated with D-Ribose-L-Cysteine are shown in Figure 4. Diabetic control rats exhibited higher serum Total cholesterol, LDL-cholesterol, triglycerides, and low HDL-cholesterol levels compared to those of normal rats. The total cholesterol, LDL- cholesterol and triglycerides levels were significantly higher (p<0.05) in diabetic control rats compared to the D-Ribose-L-Cysteine treated rats (97.50±10.50, 45.23±12.34 and 8 5.49±13.80 mg/dL), D-Ribose-L-Cysteine treated diabetic rats (105.20±7.30, 33.67±12.54 and 92.62±14.30 mg/dL), and normal control rats (110.50±7.80, 43.98±15.23 and 89.407.80, mg/dL) respectively. Whereas LDL-cholesterol levels of rats treated with D-Ribose-L-Cysteine are not significantly different when compared with the normal control rats. 3.4 Effect of D-Ribose-L-Cysteine on Sperm Parameters in STZ Induced Diabetic Rats The mean percentage of sperm motility after 28 days of treatment is shown in Figure 5. Sperm motility in the diabetic control group (35.3±7.5%) was significantly lower (p<0.05) when compared to the normal control group (87.7±9.1%). Treatment of diabetic group with D-Ribose-L- Cysteine produced a more pronounced effect with an increased in sperm motility (69.5 ±9.6%). The movement of sperm in D-Ribose-L-Cysteine treated group were similar to the normal control group (Fig. 5). As shown in Figure 5, Streptozotocin-induced diabetic control group showed a significant decreased (p<0.05) in sperm morphology (37.6±6.3%) as compared with the normal control group (84.2±6.9). There was significantly increased (p<0.05) in mean sperm morphology in D-Ribose-L-Cysteine treated group and D- Ribose-L-Cysteine treated diabetic group (85.90 ± 7.00 and 70.0±10.1) in comparison with the diabetic control group (Fig. 5). There was a significant decreased in sperm count value in the diabetic control group (33.5± 7.50, p<0.05) when compared with normal control group ((86.8± 7.70), D-Ribose-L-Cysteine treated rats (93.7±7.00) and D-Ribose-L- Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 15 Cysteine treated diabetic rats (75.5± 7.11.8) (Fig. 5). 3.5 Effect of D-Ribose-L-Cysteine on Reproductive Hormones in STZ Induced Diabetic Rats Testosterone levels decreased significantly (p < 0.05) in diabetic group compared to non-diabetic normal control. There was no significant difference in testosterone levels of animals that received D-Ribose-L-Cysteine compared with normal control, but it increased significantly (p < 0.05) compared to diabetic control group (Fig. 6). There was no significant difference in FSH of normal control and D-Ribose-L-Cysteine groups; however, there was a significant increase of FSH in animals that received D-Ribose-L-Cysteine group and D-Ribose-L-Cysteine diabetic group compared to diabetic group (Fig. 6). Luteinizing hormone levels increased significantly (p < 0.05) in the D-Ribose-L- Cysteine group compared to diabetic control groups. However, diabetic animals administered D-Ribose-L-Cysteine had significantly decreased (p < 0.05) levels of LH compared to normal control. FSH decreased significantly (p < 0.05) in the diabetic control group and compared with non-diabetic normal control (Fig. 6). NC DC DRC DRCD 0 50 100 150 200 250 Initial Final * * ** Parameters Figure 1: Effect of D-Ribose-L-Cysteine on Body weight in STZ induced diabetic rats. Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05). ** Significantly different from normal and diabetic controls (p<0.05). NC: Normal Control, DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD: D-Ribose-L-Cysteine treated diabetic rats W ei gh t (g ) NC DC DRC DRCD 0 100 200 300 400 500 Initial Final * ** Figure 2a: Effect of D-Ribose-L-Cysteine on blood glucose in STZ induced diabetic rats. Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05). ** Significantly different from normal and diabetic controls (p<0.05).  Significantly different from Initial Fasting Blood glucose (p<0.05) NC: Normal Control, DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD: D-Ribose-L-Cysteine treated diabetic rats F as ti ng b lo o d g lu co se ( m gd l-1 ) Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 16 NC DC DRC DRCD 0 5 10 15 20 ** ** * Figure 2b: Effect of D-Ribose-L-Cyste ine on serum glucose in STZ induced diabetic rats. Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05). ** Significantly different from normal and diabetic controls (p<0.05). NC: Normal Control, DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD: D-Ribose-L-Cysteine treated diabetic rats S er um c on ce nt ra ti on (m m ol L -1 ) 0 2 4 6 8 10 NC DC DRC DRCD * ** ** MDA Figure 3: Effect of D-Ribose-L-Cysteine on lipid peroxidation in STZ induced diabetic rats. Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05). ** Significantly different from normal and diabetic controls (p<0.05). NC: Normal Control, DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats , DRCD: D-Ribose-L-Cysteine treated diabetic rats C on ce nt ra ti on ( nm ol m l-1 ) TC HDL-C LDL-C TG 0 50 100 150 NC DC DRC DRCD * ** * * ** ** * * * * * Figure 4: Effect of D-Ribose-L-Cysteine on lipid profile in STZ induced diabetic rats. Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05). ** Significantly different from normal and diabetic controls (p<0.05). NC: Normal Control, DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD: D-Ribose-L-Cysteine treated diabetic rats. TC: Total Cholesterol, HDL-C: High density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol TG: Triglycerides C o n ce nt ra ti on ( m gd L -1 ) Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 17 TT (ngdl-1) FSH (miuL-1) LH (miuL-1) 0 2 4 6 8 10 NC DC DRC DRCD * * * ** ** ** ** ** Figure 6: Effect of D-Ribose-L-Cysteine on reproductive hormone in STZ induced diabetic rats. Values are expressed as Mean ± SD, * signif icantly different from normal control group (p<0.05). ** Signif icantly dif ferent from normal and diabetic controls (p<0.05). NC: Normal Control, DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD: D-Ribose-L-Cysteine treated diabetic rats. TT: Testosterone, FSH: Follicle stimulating hormone, LH: Lutenizing hormone C o n c e n tr a ti o n 4. DISCUSSION Diabetes mellitus is a chronic metabolic disease with debilitating complications. Two types are mostly described in the literature; type 1(insulin- dependent diabetes mellitus) and type-2 (insulin- resistant diabetes mellitus) [1]. These two interestingly, though have distinct pathogenesis, share similar life-threatening complications such as long-term hyperglycemia, which is associated with many other complications, including male reproductive dysfunctions and infertility [29]. Over 90% of diabetic patients are known to suffer from severe insulin resistance, which leads to severe metabolic and reproductive complications [30,31]. Hwang et al. [32] and Chen et al. [33] in a different study reported the toxic effects of STZ on pancreatic beta cells. These effects lead to a decrease in insulin production as well as less cellular absorption of glucose resulting in glucose toxicity, increased ROS and beta cells apoptosis. Hence, the usage of chemical substances that will aid the cellular sensitivity to insulin consequently ameliorate and prevent glucose toxicity [34]. The present study aims to investigate the ameliorative effect of D-Ribose-L- Cysteine on the blood glucose, lipid peroxidation, lipid profile and reproductive system in adult male Wistar rats. Kalaiarasi and Pugalendi [35] reported a severe loss in body weight in streptozotocin-induced diabetes. The decrease in the bodyweight of diabetic rats in this study was due to the cytotoxic effects of streptozotocin on cells leading to loss or degradation of structural Motility (%) Morphology (%) Sperm count (x106/ml) 0 50 100 150 NC DC DRC DRCD * ** * ** * ** Figure 5:Effect of D-Ribose-L-Cysteine on Sperm parameters in STZ induced diabetic rats. Values are expressed as Mean ± SD, * significantly different from normal control group (p<0.05). ** Significantly different from normal and diabetic controls (p<0.05). NC: Normal Control, DC: Diabetic control, DRC: D-Ribose-L-Cysteine treated rats, DRCD: D-Ribose-L-Cysteine treated diabetic rats Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 18 proteins to provide amino acids for gluconeogenesis during insulin deficiency resulting to muscle wasting and weight loss. The protein content is decreased in muscular tissue by proteolysis due to insulin deficiency [36]. In the present study, diabetic control rats showed a marked reduction in their body weights when compared to normal control rats. The weight loss was reversed by the administration of D-Ribose- L-Cysteine to the diabetic rats. In addition, glucose reacts with proteins in a non-enzymatic manner leading to the development of Amadori products followed by the formation of advanced glycation end-products AGEs; ROS is generated at multiple steps during this process [37]. Elevated lipid peroxidation in tissues will result in a concomitant decrease in body weights [38] as seen in this study. D-Ribose-L-Cysteine administered maintained the body weights of the animals protecting them from the cytotoxic effects of streptozotocin. These results suggest a possibility of D-Ribose-L-Cysteine to either improve pancreatic beta cells function or prevent lipid peroxidation by impairing the formation of ROS or increasing the production of antioxidants to neutralize ROS generated. Increased oxidative stress and changes in the antioxidant capacity as observed in this study have been implicated in the etiology of chronic diabetes complications as reported by Van et al. [39] and Omotayo et al. [38]. This study demonstrated that streptozotocin increased lipid peroxidation. The elevated levels of oxidative stress markers have been associated with hyperglycemia which is due to the shortfall in insulin as a result of beta cell dysfunction [40,41]. This anomaly has been associated with complications including cardiovascular diseases in diabetes mellitus as reported by Omotayo et al. [38] and George et al. [42]. These negative effects of streptozotocin were ameliorated by D-Ribose-L-Cysteine. Since streptozotocin is known to destroy pancreatic beta cells leading to a concomitant increase in glucose availability- hyperglycemia [43], therefore, the possible mechanism of action of D- Ribose-L-Cysteine is mediated through influencing glucose uptake or utilization by tissues and probably regeneration of beta cells. Hyperglycemia may result in glucose toxicity and increase in ROS activity as well as increased lipid peroxidation especially in the pancreas with low antioxidants level [44]. This is in tandem with the increased serum MDA levels of the diabetic controls rats in this study. Furthermore, the decreased MDA levels as seen in animals that received D-Ribose-L-Cysteine showed an abrogation of cellular redox. In this study, there was an increased in total cholesterol, LDL-cholesterol, triacylglycerides, and low HDL-cholesterol in diabetic rats, confirming the development of dyslipidemia which is supported by previous studies [45,46]. Insulin deficiency in diabetes mellitus results in increased lipolysis and subsequent �-oxidation of acetyl-CoA, a key enzyme in cholesterol biosynthesis used in lipogenesis together with HMG-CoA reductase [46], thereby promoting the hepatic formation of VLDL-cholesterol and consequently increasing serum levels of cholesterol and LDL-cholesterol. Fatty acids that are not �-oxidated are esterified into triacylglycerols which are incorporated into VLDL-cholesterol in the liver and exported to the bloodstream [47]. These metabolic events increased lipoproteins to a value above normal in the present study, identifying dyslipidemia as a risk factor for the development of atherosclerosis [46]. Improved dyslipidemia in diabetic rats treated with D-Ribose-L-Cysteine can be explained by the greater insulin secretion in the presence of this antioxidant, D-Ribose-L- Cysteine, since insulin decreases blood sugar levels and lipolysis in adipose tissue. Studies have shown that D-Ribose-L-Cysteine increases insulin secretion. On the other hand, Ayyasamy and Leelavinothan [46] revealed that insulin increases the activity of lipoprotein lipase, which catalyzes the breakdown of triacylglycerol ester bonds thereby increasing the clearance of VLDL- cholesterol. Also, the increased insulin level as seen in diabetic control rats elevates the activity of lecithin cholesterol acyltransferase and the enzyme responsible for extracellular cholesterol esterification, thus increasing the efficiency of reverse cholesterol transport, indicating an inverse correlation with cardiovascular accidents [48,46]. Studies have identified a relationship between antioxidants and reduced cholesterol levels, due to inhibition of HMG-CoA reductase activity and cholesterol biosynthesis [49,46]. Thus, the D-Ribose-L-Cysteine administered in diabetic rats was able to normalize the atherogenic index because it was possible to control the lipid profile, a finding that is corroborated by Yang et al. [50], who reported that an increased atherogenic index is related to low antioxidant activity. Thus, D-Ribose-L- Cysteine was able to reduce the formation of atherosclerotic plaque by lowering blood glucose Adedeji and Orisadiran; AJI, 3(1): 11-22, 2020; Article no.AJI.53370 19 levels, the glycation of LDL-cholesterol, and its consequent oxidation in the present study. The increased antioxidant levels by D-Ribose-L- Cysteine in diabetic rats enhanced the production of FSH and LH by the anterior pituitary gland [51] which promotes follicle development and testosterone synthesis. Administration of D-Ribose-L-Cysteine in the study was found to improve the percentage sperm motility and sperm count. The antioxidant activity of this substance may be attributed to the reduction or amelioration of oxidative-stress induced diabetic complications such as lipid peroxidation, by elevation of antioxidant enzyme activities as observed from this study. In addition, previous studies involving treatments with antioxidant compounds demonstrate their importance in regulating β- pancreatic cell functions and growth, thereby reducing the complications due to diabetes [52,53]. The antioxidant activities of D-Ribose-L-Cysteine may also be responsible for the restoration of β- cells’ integrity and metabolic functions, while at the same time ensuring maximum synthesis of insulin by these cells necessary for glucose tolerance [52]. Therefore, helps to reverse the reproductive dysfunctions associated with diabetes as seen in the present study [54,55]. This study further strengthens previous findings by Ballester et al. [56] and Suthagar et al. [57] that intraperitoneal administration of high doses of alloxan in male rats induces type-1 diabetogenic conditions, which leads to reproductive complications such as reduced testicular and epididymal weights, decreased testosterone production, reduced sperm motility and sperm counts, and also decrease in the gonadal function of both leydig (testosterone producing) cells and sertoli (supporting) cells. 5. CONCLUSION In conclusion, D-Ribose-L-Cysteine therefore, revealed in the current study to attenuate the oxidative stress in streptozotocin-induced diabetic rats on blood glucose, lipid profile, spermatogenesis, and steroidogenesis. D- Ribose-L-Cysteine could be used as adjuvant therapy for the reduction of atherosclerosis and infertility in diabetic subject because of its potent antioxidant property. CONSENT It is not applicable. 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