Moringa oleifera-based feed supplement protects against renal ischaemia/reperfusion injury via downregulation of Bax/caspase 3 signaling.

Introduction: Ischaemia/reperfusion (I/R) may lead to acute kidney injury via the induction of oxidative stress. On the other hand, Moringa oleifera has been reported to exert antioxidant activities. This study was designed to assess whether or not Moringa oleifera-based feed supplement could prevent I/R-induced renal injury. Materials and methods: Renal I/R was induced by occluding the right renal artery for 30 min followed by a 2-h reperfusion. Results: Renal I/R led to increased absolute renal weight and renal organo-somatic weight index. Renal I/R also caused distortion of renal histoarchitecture and impaired renal function evidenced by elevated serum creatinine and blood urea nitrogen. In addition, renal I/R significantly elevated renal levels of hydrogen peroxide, MDA, and advanced oxidation protein products, but suppressed the levels of reduced glutathione, protein thiol, and non-protein thiol, and the activities of superoxide dismutase and glutathione peroxidase. In addition, renal I/R up-regulated myeloperoxidase activity and the renal levels of NO, TNF-α, and IL-6. Renal I/R also up-regulated Bax and caspase 3 expression in the kidney. Furthermore, I/R-driven structural and biochemical alterations were markedly inhibited by Moringa oleifera-based feed supplement. Discussion: These results suggest that Moringa oleifera-based feed supplement may preserve the gross and histoarchitectural integrity of the kidney as well as renal function via downregulation of Bax/caspase 3 signaling by targeting oxidative stress, inflammation and apoptosis in the kidney of I/R rat.

L-Arginine abrogates maternal and pre-pubertal codeine exposure-induced impaired spermatogenesis and sperm quality by modulating the levels of mRNA encoding spermatogenic genes.

Introduction: Although, codeine has been demonstrated to lower sperm quality; the effects of maternal and prepubertal codeine exposure on male offspring is yet to be reported. In addition, the effect of arginine on codeine-induced decline in sperm quality has not been explored. This study investigated the impact of maternal and prepubertal codeine exposure on spermatogenesis and sperm quality in F1 male Wistar rats to study the effect that codeine may have during recreational use in humans. Also, the effect of arginine supplementation on codeine-induced alteration in spermatogenesis and sperm quality was evaluated. Methods: Female rats were treated with either 0.5 ml distilled water or codeine orally for eight weeks, and then mated with male rats (female:male, 2:1). The F1 male offsprings of both cohorts were weaned at 3 weeks old and administered distilled water, codeine, arginine, or codeine with arginine orally for eight weeks. Results: Prepubertal codeine exposure in rats whose dams (female parents) were exposed to codeine delayed puberty and reduced the weight at puberty. Prepubertal codeine exposure exacerbated maternal codeine exposure-induced reduced total and daily spermatid production, sperm count, sperm motility, and normal sperm form, as well as impaired sperm plasma membrane integrity and increased not intact acrosome and damaged sperm DNA integrity. These perturbations were accompanied by a decrease in mRNA levels encoding spermatogenic genes, testicular testosterone and androgen receptor (AR) concentrations, and upregulation of sperm 8-hydroxydeoxyguanosine (8OHdG). Prepubertal arginine supplementation mitigated codeine-induced alterations. Discussion: This study provides novel experimental evidence that maternal and prepubertal codeine exposure reprogramed spermatogenesis and sperm quality of male FI generation by decreasing mRNA levels encoding spermatogenic genes and AR via oxidative stress-mediated signaling, which was abrogated by prepubertal arginine supplementation.

Evaluation of testicular torsion management in Ogbomoso, South-Western Nigeria and surgical detorsion-augmented treatment with phytochemical fractions of Corchorus olitorius leaf in experimental rats.

Background: There is need to investigate whether phytochemicals along with surgical detorsion could serve as better managements options in TT patients rather than surgical detorsion (SD) alone. Methods: The descriptive cross-sectional part of this study is questionnaire-based addressing sociodemographic characteristics of participants and their experience in management of TT. In the experimental part, male rats (n = 32) were grouped into: sham, Ischemia-reperfusion injury (IRI), dichloromethane (DCM) and ethanol fraction (100 mg/kg) of CO. Evaluation of tissue GPx, total thiol, SOD, MDA and H2O2 was done. Serum estimations of nitrite, TNF-α and IL-6, MPO, sperm motility, count and viability was also carried out. Tissue expression of bax and caspase 3 was assessed. Results: 68.9 % respondents agreed that SD alone is non-effective in the management of TT while 83.6 % reported a need to augment surgery with medications. Oxidative stress markers like H2O2, MDA and nitrite increased by IRI were decreased in post-treatment groups, along with a significant increase in the tissue level of GSH, GST, SOD, GPx, and total thiol. Inflammatory mediators were elevated in IRI while post-treatment rats showed significant decrease. IRI decreased sperm count significantly this was reversed by post-treatment. Bax and caspase 3 was increased in IRI rats and post-treatment with CO fractions reduced them. Conclusions: Quantitative cross-sectional study has revealed through experience of clinicians that surgical detorsion alone is not effective in managing TT. Augmented treatment with CO leaf fractions suppressed testicular IRI through inhibition of pro-apoptotic proteins expression, oxidative stress and inflammation.

Cysteamine Attenuate Intestinal Reperfusion Injury Induced by Occlusion of Mesenteric Artery by Enhancing Intracellular Thiol Activities.

BACKGROUND: Ischemia/reperfusion has been reported to further damage the intestine reperfusion injury (IRI) and cause multiple distal organ dysfunction through oxidative stress, inflammation, and apoptosis. Cysteamine is known to inhibit oxidative stress, inflammatory cytokines and apoptosis. This experiment was designed to evaluate the role of cysteamine against IRI in rats METHODS: Thirty-two Wistar rat strains were assigned to four groups: sham, Intestinal-reperfusion injury (IRI), 50 mg/kg and 100 mg/kg cysteamine treatment IRI. A 5 cm segment of terminal ileum was twisted 360° clockwise along the mesentery for 45 minutes to induce ischemia before detorsion. Tissues were preserved for biochemical evaluation and histology 4 hours after detorsion. Activities of GPx, GSH, protein and non-protein thiol, H2O2, MDA were evaluated. Serum concentration of nitrite, MPO, ALT, AST TNF-alpha and IL-6 were measured. Caspase 3 and bax were evaluated by immunohistochemistry. Statistical significance was set as p<0.05 RESULTS: Significant (p<0.05) increase in H2O2, MDA and nitrite but reduction in GPx, GSH, protein thiol and non-protein thiol in the IRI rats was reversed by 50 and 100 mg/kg cysteamine. Serum MPO, TNF-α, IL6, AST and ALT was significantly elevated in IRI while the rats treated with cysteamine showed a significant decrease (p<0.05) in the activities of these inflammatory and hepatic injury markers. CONCLUSION: Cysteamine mitigate IRI by enhancing intracellular antioxidant defense system, inhibiting inflammatory mediators and intestinal tissue expression of pro-apoptotic protein.

L-Arginine reverses maternal and pre-pubertal codeine exposure-induced sexual dysfunction via upregulation of androgen receptor gene and NO/cGMP signaling.

BACKGROUND: Although codeine has been reported to enhance sexual activity by improving penile reflexes, it has been shown to impair fertility indices. Also, codeine impairs ovarian steroidogenesis and folliculogenesis. Nonetheless, whether or not codeine exerts an epigenetic effect remains unclear. On the other hand, arginine has been speculated to enhance penile reflexes by upregulating NO/cGMP Signaling. AIM: The study evaluated the effect of maternal codeine exposure and prepubertal codeine and arginine treatments on F1 male sexual function and fertility indices, as well as the outcome of F2 progenies. In addition, the epigenetic programming mechanism was also explored. METHODS: Forty three-week-old female rats were randomized into two groups (n = 20 rats/group); the control that received 0.5 ml of distilled water and the codeine-treated that received 5 mg/kg of codeine via gavage for eight weeks. Afterward, the female rats were paired for mating with sexually mature male rats. Rats were maintained on their pre-pregnancy treatments throughout pregnancy and lactation. FI progenies from each cohort (control and codeine-treated cohorts) were weaned at three weeks and randomized into four groups; the control, codeine-treated, L-arginine-treated (300mg/kg), and codeine + L-arginine-treated (n = 10 rats/group). Administration commenced a week post-weaning and lasted for eight weeks via gavage. KEY FINDINGS: Maternal codeine exposure did not alter body weight, but significantly reduced anogenital distance and anogenital index of F1 male offspring. Also, maternal codeine delayed preputial membrane separation, impaired male sexual competence, and penile reflexes of F1 male offsprings. These were associated with reduced dopamine, gonadotropins, and testosterone levels as well as suppressed expression of androgen receptor mRNA. In addition, maternal codeine downregulated NO/cGMP signaling, impaired fertility indices, and reduced the litter size, weight, and survival of F2 progenies. These alterations were observed to be aggravated by prepubertal codeine exposure but improved by prepubertal arginine treatment. SIGNIFICANCE: In conclusion, codeine programmed sexual dysfunction by suppressing the levels of dopamine and testosterone, as well as repressing the expression of androgen receptor mRNA. In addition, codeine-induced epigenetic reprogramming was expressed in the F2 offsprings as reduced litter size and weight, and survival rate. Notably, these observations were worsened by prepubertal codeine exposure, but dampened by prepubertal arginine treatment.

Cysteamine mitigates torsion/detorsion-induced reperfusion injury via inhibition of apoptosis, oxidative stress and inflammatory responses in experimental rat model.

Oxidative stress, inflammation and apoptosis are major pathways in pathophysiology of testicular torsion/detorsion (TTDT) reperfusion injury. This study evaluated the antioxidant, anti-inflammatory and anti-apoptotic role of cysteamine in TTDT-induced injury. Male Wistar rats (n = 32) were grouped into four (n = 8): sham, ischaemia-reperfusion injury (IRI), cysteamine (100 mg/kg and 200 mg/kg) for in vivo study. Samples were taken for biomolecular and histological evaluation 48 hr after detorsion. Tissue SOD, GPx, GSH, GST activity, total thiol, H2 O2 and MDA were assessed. Serum levels of NO, MPO, TNF-alpha and IL-6 and sperm motility, count and viability were assessed. Caspase-3 and bax were evaluated by immunohistochemistry. Significant difference was set as p < .05. Significant increase in H2 O2, MDA and nitrite but reduction in SOD, GPx, GSH, GST and total thiol in the testicular tissue of IRI rats was reversed by cysteamine. Serum MPO and TNF-α were significantly elevated in RI, while treated-RI rats showed decrease (p < .05) in tissue level of the inflammation markers. Reduced sperm motility in RI was significantly reversed by cysteamine. Increased tissue expression of bax and caspase-3 was reversed by cysteamine. Cysteamine protected the testis against reperfusion injury through anti-inflammatory, antioxidant effects and inhibition of apoptosis in rats.

High-fat diet reduces weight gain but increases other cardio-metabolic indices in offspring of normotensive and hypertensive rats.

This study investigated the effect of post-natal consumption of high-fat diet (HFD) on cardio-metabolic indices in male offspring of hypertensive female rats. There were neither significant differences in body weight gain either in pups from normotensive or hypertensive dams that received normal diet during the post-weaning periods (except at 7th and 9th weeks), nor in both pup groups that received HFD. However, both pup groups that received HFD had reduced body weight gain when compared to their counterparts that received normal diet. Post-weaning administration of HFD to pups of hypertensive and normotensive dams significantly increased their blood glucose, pressure and lipid profiles when compared to those weaned to normal diet. It was concluded that male offspring consumption of HFD diet elicits cardio-metabolic disturbance that slightly depended of maternal cardiovascular status but majorly depended on post-weaning weight gain, while that elicited by maternal hypertension is not related to post-weaning weight gain.