Allopurinol and Febuxostat Equally Attenuate Methotrexate-Induced Testicular Injury In Rats Via Activation Of EGF/ ERK1/2/HO‐1 Signaling Pathway.

Methotrexate (MTX) is commonly used in the management of several malignancies and autoimmune disorders; however, testicular damage is one of the most detrimental effects of MTX administration. In the current study, we evaluated the possible protective effect of xanthine oxidase inhibitors either purine analogue; allopurinol (ALL) or non-purine analogue; febuxostat (FEB) in testicular injury induced by MTX in rats. Gonadotoxicity was induced by a single dose of MTX (20 mg/kg, i.p.). ALL and FEB were administered orally in the following daily doses (100, 10 mg/kg, respectively) for 15 days. Total and free testosterone were measured in serum. In addition, total antioxidant capacity (TAC), epidermal growth factor (EGF), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), extracellular signal-regulating kinase1/2 (ERK1/2), and nitric oxide (NO) end products were measured in testicular tissues. At the same time, immunoexpression of HO-1in testicular tissue was measured. Histopathological examination was done. ALL and FEB increased total and free serum testosterone. Both drugs showed a significant reduction in testicular MDA, NO, TNF-α levels with an increase in TAC, EGF, and ERK1/2 levels in testicular tissue. Furthermore, both drugs enhanced HO-1 immunoexpression in testicular tissue. All these findings were parallel to the preservation of normal testicular architecture in rats treated with ALL and FEB. In conclusion, All and FEB were protective against testicular damage induced by MTX through anti-inflammatory, anti-apoptotic, and antioxidant actions which might be through activation of the EGF/ERK1/2/HO-1 pathway. At the same time, no significant difference between ALL and FEB was noticed in this protective effect.

Polyamine metabolism links gut microbiota and testicular dysfunction

Background Male fertility impaired by exogenous toxins is a serious worldwide issue threatening the health of the new-born and causing infertility. However, the metabolic connection between toxic exposures and testicular dysfunction remains unclear. Results In the present study, the metabolic disorder of testicular dysfunction was investigated using triptolide-induced testicular injury in mice. We found that triptolide induced spermine deficiency resulting from disruption of polyamine biosynthesis and uptake in testis, and perturbation of the gut microbiota. Supplementation with exogenous spermine reversed triptolide-induced testicular dysfunction through increasing the expression of genes related to early and late spermatogenic events, as well as increasing the reduced number of offspring. Loss of gut microbiota by antibiotic treatment resulted in depletion of spermine levels in the intestine and potentiation of testicular injury. Testicular dysfunction in triptolide-treated mice was reversed by gut microbial transplantation from untreated mice and supplementation with polyamine-producing Parabacteroides distasonis. The protective effect of spermine during testicular injury was largely dependent on upregulation of heat shock protein 70s (HSP70s) both in vivo and in vitro. Conclusions The present study linked alterations in the gut microbiota to testicular dysfunction through disruption of polyamine metabolism. The diversity and dynamics of the gut microbiota may be considered as a therapeutic option to prevent male infertility.

The Potential Protective Effect and Possible Mechanism of Peptides from Oyster (Crassostrea hongkongensis) Hydrolysate on Triptolide-Induced Testis Injury in Male Mice

Peptides from oyster hydrolysate (OPs) have a variety of biological activities. However, its protective effect and exact mechanism on testicular injury remain poorly understood. This study aimed to evaluate the protective effect of OPs on triptolide (TP)-induced testis damage and spermatogenesis dysfunction and investigate its underlying mechanism. In this work, the TP-induced testis injury model was created while OPs were gavaged in mice for 4 weeks. The results showed that OPs significantly improved the sperm count and motility of mice, and alleviated the seminiferous tubule injury. Further study showed that OPs decreased malonaldehyde (MDA) level and increased antioxidant enzyme (SOD and GPH-Px) activities, attenuating oxidative stress and thereby reducing the number of apoptotic cells in the testis. In addition, OPs improved the activities of enzymes (LDH, ALP and ACP) related to energy metabolism in the testis and restored the serum hormone level of mice to normal. Furthermore, OPs promoted the expression of Nrf2 protein, and then increased the expression of antioxidant enzyme regulatory protein (HO-1 and NQO1) in the testis. OPs inhibited JNK phosphorylation and Bcl-2/Bax-mediated apoptosis. In conclusion, OPs have a protective effect on testicular injury and spermatogenesis disorders caused by TP, suggesting the potential protection of OPs on male reproduction.

Scrotal self-inflicted gunshot injuries: report of two consecutive cases and literature review

Background Isolated scrotal gunshot injuries are uncommon. Even more so when they are self-inflicted. The extent of the injury is determined by the caliber of the weapon. Established management protocols when followed yields excellent results. Case presentations We present two male patients, aged 41 and 51 years old, who sustained gunshot injuries to the scrotum following accidental discharges from hand guns stored in their trouser pockets. The first (41 years) sustained grade 5 American Association for Surgery of Trauma (AAST) left testicular injury and was managed by unilateral orchidectomy. The second (51 years old) sustained bilateral grade 4 AAST testicular injuries and had both testes salvaged by primary repair after meticulous debridement. Conclusion Isolated scrotal gunshot injuries can occur when low velocity guns are placed adjacent to the genitalia and accidentally discharged. The testes are endangered and can be devitalized requiring orchidectomy or salvaged by meticulous debridement and primary repair when viability is not compromised.