RESUMO
Paeonol, a phenolic ingredient in the genus Paeonia, possesses antioxidant and anti-inflammatory effects. Methotrexate (MTX) is a commonly used chemotherapeutic agent; however, its germ cell damage is a critical problem. P-glycoprotein (P-gp), an efflux transporter, is a member of the blood-testis barrier. The present study evaluated the protective effect of paeonol on MTX-induced testicular injury in rats with the exploration of its mechanism and the possible contribution of P-gp in such protection. Testicular weight, serum testosterone, and testicular P-gp levels were measured. Testicular oxidant/antioxidant status was evaluated via determining the levels of malondialdehyde, total nitrite, reduced glutathione, and superoxide dismutase activity. The inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the apoptotic marker caspase 3 were estimated immunohistochemically. Testicular histopathology and spermatogenesis scores were also examined. MTX caused histopathologically evident testicular damage with decreased testicular weight, testosterone level, and spermatogenesis score, as well as significant increases in oxidative, inflammatory, and apoptotic responses. Paeonol significantly restored testicular weight, testosterone level, spermatogenesis score, and oxidant/antioxidant balance. Moreover, paeonol increased the testicular P-gp level and significantly decreased TNF-α and caspase 3 immunostaining. In conclusion, paeonol offered a protective effect against MTX-induced testicular injury through its antioxidant, anti-inflammatory, and antiapoptotic effects, as well as by increasing testicular P-gp level.
RESUMO
Chronic stress has been linked to many diseases resulted from dysfunction of both the nervous system and peripheral organ systems. Yet, the effects of chronic stress on the pancreas have received relatively little attention. This work aims to investigate the influence of chronic stress exposure on both the endocrine and exocrine pancreatic function and morphology and its possible mechanism of action, and also to evaluate the impact of chronic exercise with moderate intensity on ameliorating the stress-induced pancreatic changes. Forty adult male albino rats were used and divided into four groups: control group, exercised group (3 weeks of swimming exercise), stressed group (3 weeks of immobilization stress), and stressed group practicing exercise (3 weeks of exercise, concomitant with 21 daily sessions of stress). On the final day of the experiment, all rats were sacrificed. Biochemical, immunohistochemical, and histological studies were conducted. The results showed that chronic immobilization stress produced hyperglycemia, hyperinsulinemia, and increased homeostatic model assessment of insulin resistance index (HOMA-IR) with increasing exocrine pancreatic injury markers by increasing oxidative and inflammatory status of the pancreatic tissue. Histological study showed the injurious effect of stress on the morphology of pancreatic tissue. Physical exercise protected the pancreas from the negative effects of stress through its anti-inflammatory and anti-oxidative effects, evidenced by increasing pancreatic interleukin 10 and total antioxidant capacity and decreasing pancreatic tumor necrosis factor-alpha, and malondialdehyde with ameliorating most of the histological changes induced by stress exposure. Physical exercise effectively counteracts chronic stress-induced pancreatic changes through different mechanisms.
