Sex and dose differences in morphine administration on renal function, inflammatory and apoptotic markers in male and female Wistar rats

Abstract

This study examined the impact of morphine on renal function, antioxidant enzymes, and inflammatory and apoptotic markers in male and female Wistar rats, considering both sex- and dose-dependent effects. 40 Wistar rats (20 male, 20 female), each weighing 120-150 g were used in this study. The control group received distilled water (0.5 mL/100g b.w), while experimental groups were given morphine orally at 20, 40 and 60 mg/kg daily for 30 days. Renal function, inflammatory, and apoptotic markers were assessed in the plasma and tissue homogenate. Kidneys were preserved in 10% formo-saline for histological examination. Morphine significantly increased plasma creatinine in both male and female rats, with the increase being more pronounced in males. Caspase-3 and TNF-α were also elevated in both sexes, but with no significant difference between males and females. Male rats showed significantly higher catalase activity and elevated plasma sodium, potassium, phosphate, and chloride ion concentrations compared to females. Photomicrographs revealed that low and medium doses of morphine caused more severe kidney damage in both male and female rats, leading to atrophied glomeruli, widened Bowman's space, and loss of brush border in the tubules. Conversely, high-dose resulted in less pronounced damage, with only a few atrophied glomeruli and indistinct tubules. Morphine induced more pronounced lipid peroxidation and oxidative stress in female rats compared to males, as indicated by changes in their plasma electrolytes and antioxidant enzyme activities. Interestingly, lower dose caused more significant alterations in renal function, oxidative stress and apoptotic markers compared to medium and high doses. • Female rat kidneys are more susceptible than male rat kidneys to morphine-induced oxidative stress, plasma electrolyte alterations, and lipid peroxidation. • Females had better glomerular protection than males, an effect linked to differences in sexual steroid hormones. • Tumor necrosis factor and caspase-3 levels did not differ significantly between males and females. • Morphine's impact on renal function isn't dose dependent.