Impact of stress on male fertility: role of gonadotropin inhibitory hormone.

Studies have implicated oxidative stress-sensitive signaling in the pathogenesis of stress-induced male infertility. However, apart from oxidative stress, gonadotropin inhibitory hormone (GnIH) plays a major role. The present study provides a detailed review of the role of GnIH in stress-induced male infertility. Available evidence-based data revealed that GnIH enhances the release of corticosteroids by activating the hypothalamic-pituitary-adrenal axis. GnIH also mediates the inhibition of the conversion of thyroxine (T4) to triiodothyronine (T3) by suppressing the hypothalamic-pituitary-thyroidal axis. In addition, GnIH inhibits gonadotropin-releasing hormone (GnRH), thus suppressing the hypothalamic-pituitary-testicular axis, and by extension testosterone biosynthesis. More so, GnIH inhibits kisspeptin release. These events distort testicular histoarchitecture, impair testicular and adrenal steroidogenesis, lower spermatogenesis, and deteriorate sperm quality and function. In conclusion, GnIH, via multiple mechanisms, plays a key role in stress-induced male infertility. Suppression of GnIH under stressful conditions may thus be a beneficial prophylactic and/or therapeutic strategy.

Elevated reproductive toxicity effects of diclofenac after withdrawal: Investigation of the therapeutic role of melatonin.

Although there are several reports on the toxic actions of sodium diclofenac (DF), there is dearth information on its effect on the male reproductive system. Therefore, the study investigated the effects of DF and melatonin in male rats. Twenty rats were used in this study, which lasted for 6 weeks. The control group (vehicle treated) received normal saline (0.1 ml/day, p.o.). In the experimental groups, DF was administered during the first (group 2) and last (group 3) three weeks of the study. However, in group 4, melatonin was administered for 3 weeks, after 3 weeks of treatment with DF. DF and melatonin were administered at 1 and 10 mg/kg b.w./day (p.o.) respectively. The results showed that unlike melatonin, DF had no effect on gonadotrophins; however, it caused significant decreases in GNRH and testosterone, but a significant increase in prolactin. Melatonin attenuated the pro-antioxidant and pro-inflammatory effects of DF, which caused significant decreases in SOD, TAC, CAT, but significant elevations in LDH, MDA, uric acid and CRP. Moreover, the hormone reversed the adverse effect of DF on sperm count, sperm motility and sperm morphology. There were slight evidence of the precipitation of imbalance in lipid metabolism by DF and the antidyslipidaemic action of melatonin. Compared to DF, DF recovery showed more adverse effects on prolactin, testosterone, LDH, MDA, UA, CRP, semen parameters (except sperm motility), TC, LDL-c, HDL-c and phospholipid. The histological results agreed with the biochemical assays. In conclusion, the reproductive toxicity effects of DF seem to escalate after withdrawal; however, these effects could be attenuated by treatment with melatonin.

Additive and nonadditive effects of salmon calcitonin and omega-3 fatty acids on antioxidant, hematological and bone and cartilage markers in experimental diabetic-osteoarthritic rats.

Reports on the coexistence of diabetes mellitus and osteoarthritis in human subjects dated back to the 1960s. However, there is no account in literature on the co-manifestation of these disease conditions in experimental animals. In our previous study, we reported for the first time, the effects of pharmacological agents on glucoregulatory indices, lipid profile, and inflammatory markers in experimental diabetic-knee osteoarthritic rat. However, in the present study, the effects of salmon calcitonin (Sct), and/or omega-3 fatty acids (N-3) were further investigated on other biomarkers. Forty-nine rats of seven animals per group were used for this study. Diabetes was induced by the administration of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). Thereafter, knee osteoarthritis was induced by the intra-articular injection of 4 mg of sodium monoiodoacetate in 40 µl of saline. Nine days after the inductions, treatments started, and they lasted for 4 weeks. N-3 was administered at 200 mg/kg/day, while Sct was administered at 2.5 and 5.0 IU/kg/day. The results of the study indicated that the induced diabetes-knee osteoarthritis caused significant alterations in all the observed biomarkers. Sct showed a dose-specific effect and an additive action with N-3 in reducing malondialdehyde and lactate dehydrogenase, and in elevating total bilirubin and total antioxidant capacity. However, it largely demonstrated a nondose-specific effect and nonadditive action with N-3 on superoxide dismutase, catalase, glutathione peroxidase, total alkaline phosphatase, c-telopeptide of type-I collagen, collagen type-2 alpha 1, and hematological indices. In conclusion, the combined administration of Sct and N-3 proffer better therapeutic effects than the single therapy; therefore, they could be used in the management of diabetic-osteoarthritic condition.

Effects of single or combined administration of salmon calcitonin and omega-3 fatty acids vs. diclofenac sodium in sodium monoiodoacetate-induced knee osteoarthritis in male Wistar rats.

BACKGROUND: There is a continuous search for a better therapy in osteoarthritis (OA) management. Therefore, this study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids (N-3) relative to diclofenac sodium (DF) in induced knee osteoarthritic male Wistar rats. METHODS: The 40 rats that were used in this study were divided into 8 groups (n=5 rats), viz: Normal control; OA control; OA+N-3; OA+Low dose of Sct (Sct.Lw); OA+High dose of Sct (Sct.Hi); OA+N-3+SCt.Lw; OA+N-3+Sct.Hi; and, OA+DF. OA was induced with 4 mg of sodium monoiodoacetate in 40 µL of saline. The solution was injected into the left knee joint space of anaesthetised rats. Sct was administered at 2.5 and 5.0 IU/kg b.w. (im), whereas N-3 and DF were administered at 200 and 1 mg/kg b.w. (p.o.), respectively. Treatments commenced 9 days after the induction of OA, and they lasted for 28 days. RESULTS: Sct and/or N-3 significantly reduced c-telopeptide of type 1 collagen (CTX-1), collagen type 2 α-1 (C2M), malondialdehyde (MDA), uric acid (UA), and interleukin-6 (IL-6), but, significantly increased superoxide dismutase (SOD) after OA induction. Both therapies had additive effects on C2M, MDA, SOD, and catalase (CAT), but, non-additive actions on UA, IL-6, and CTX-1. Like the Sct and N-3, DF significantly reduced CTX-1, C2M, UA, and IL-6. However, it had no significant effect on SOD and MDA, even though it significantly reduced CAT activity. None of the therapies had significant effect on total alkaline phosphatase activity, except N-3+Sct.Lw. CONCLUSIONS: The combined, and sometimes the single administration of Sct and N-3 proved to be better therapies in OA management than DF.

Effects of single or combined induction of diabetes mellitus and knee osteoarthritis on some biochemical and haematological parameters in rats.

Clinical evidences on the coexistence of diabetes mellitus (DM) and osteoarthritis (OA) dated back to the 1960s. Therefore, the study investigated the effects of induced DM and/or knee osteoarthritis (KOA) on some biochemical and haematological parameters in adult male Wistar rats. Twenty rats were used for this study. They were randomly divided into 4 groups (N=5 rats) which included: Normal control; Osteoarthritic (OA) control; Diabetic control; and, Diabetic+Osteoarthritic (D+OA) control. DM was induced in overnight fasted rats by the administration of streptozotocin (65mg/kg b.w., i.p.) 15min after the administration of nicotinamide (110mg/kg, b.w., i.p.). However, KOA was induced by the intra-articular injection of 4mg of sodium monoiodoacetate in 40µl of normal saline. In the D+OA group, KOA was induced about 12h after the induction of DM. The rats were left untreated for four weeks. Afterwards, the experiment was terminated. The results showed that both DM and OA featured hypercortisolism and dyslipidaemia. The additive effects of both conditions were observed on the lipid profile and some haematological indices in the D+OA group. Unlike DM, OA had mild adverse effects on the haematological profile. Nevertheless, it significantly contributed to hyperglycaemia in the D+OA group, even though it had no significant effect on the insulin resistance. However, the hypocalcaemic and glycogenolytic effects of DM were negated by OA. In conclusion, the coexistence of DM and OA presents a greater challenge on the biochemical and haematological profiles than the individual disease. But, this prediction could sometimes be annulled by the intervention of endogenous homeostatic mechanisms.

Melatonin and vitamin C exacerbate Cannabis sativa-induced testicular damage when administered separately but ameliorate it when combined in rats.

BACKGROUND: The mechanisms involved in the spermatotoxic effect of Cannabis sativa are inconclusive. The involvement of oxidative stress in male factor infertility has been well documented, and the antioxidative potential of melatonin and vitamin C in many oxidative stress conditions has been well reported. This study sought to investigate whether melatonin and vitamin C will ameliorate C. sativa-induced spermatotoxicity or not. METHODS: Fifty-five (55) male albino rats (250-300 g) were randomly divided in a blinded fashion into five oral treatment groups as follows: group I (control, n=5) received 1 mL/kg of 10% ethanol for 30 days; groups IIa, IIb, and IIc (n=5 each) received 2 mg/kg C. sativa for 20, 30, and 40 days, respectively; groups IIIa, IIIb, and IIIc (n=5 each) received a combination of 2 mg/kg C. sativa and 4 mg/kg melatonin for 20, 30, and 40 days, respectively; groups IVa, IVb, and IVc (n=5 each) received a combination of 2 mg/kg C. sativa and 1.25 g/kg vitamin C for 20, 30, and 40 days, respectively; group V (n=5) received a combination of 2 mg/kg C. sativa, 4 mg/kg melatonin, and 1.25 g/kg vitamin C for 30 days. RESULTS: Cannabis treatments reduced the Johnsen score, sperm count, motility, morphology, paired testicular/body weight ratio, and total antioxidant capacity, but increased lactate dehydrogenase activity. In addition, supplementation of cannabis-treated rats with either melatonin or vitamin C exacerbates the effect of cannabis on those parameters, whereas combination of melatonin and vitamin C reversed the trend to the level comparable to control. CONCLUSIONS: This study further showed the gonadotoxic effect of C. sativa, which could be mediated by oxidative stress. It also showed that melatonin and vitamin C exacerbate C. sativa-induced testicular damage when administered separately but ameliorate it when combined in rats.

Methanolic extract of Moringa oleifera leaves improves glucose tolerance, glycogen synthesis and lipid metabolism in alloxan-induced diabetic rats.

BACKGROUND: Glucose-lowering effects of Moringa oleifera extracts have been reported. However, the mechanism for its hypoglycemic effects is not yet understood. This study investigated the effect of oral administration of methanolic extracts of M. oleifera (MOLE) on glucose tolerance, glycogen synthesis, and lipid metabolism in rats with alloxan-induced diabetes. METHODS: MOLE was screened for key phytochemicals and its total flavonoids and phenolic contents were quantified. Diabetes was induced by intraperitoneal injection of 120 mg/kg BW alloxan. Normal and diabetic control rats received saline, while rats in other groups received 300 or 600 mg/kg body weight of MOLE or metformin (100 mg/kg body weight of metformin) for 6 weeks. Food intake and body weight were monitored throughout the experiment. Intraperitoneal glucose tolerance was assessed and serum glucose, insulin, and lipids were measured at the end of the experiment. Liver and muscle glycogen synthase activities, glycogen content, and glucose uptake were determined. RESULTS: Administration of MOLE did not affect food intake but inhibited weight loss, significantly (p<0.01) improved glucose tolerance, and increased serum insulin levels by 1.3-1.7-fold (p<0.01). MOLE treatment significantly (p<0.001) reduced serum concentrations of triglyceride, total cholesterol, and low-density lipoprotein (LDL)-cholesterol and enhanced serum level of high-density lipoprotein (HDL) by 2.4- to 3.2-fold (p<0.001). Glycogen synthase activities and glycogen contents were higher in MOLE-treated rats compared with rats receiving metformin or saline and the extract improved glucose uptake by 49%-59% (p<0.01). CONCLUSIONS: These results showed that hypoglycemic effects of MOLE might be mediated through the stimulation of insulin release leading to enhanced glucose uptake and glycogen synthesis.