Olukiran Olaoluwa Sesan, Ogundipe Oluwadare Joshua, Adelodun Stephen Taiye, Hamed Moses Agbomhere, Babatunde Olayemi Sola, Alese Oluwole Ojo, Akomolafe Rufus Ojo
Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile Ife, Nigeria.
Department of Physiology, Osun State University, Osogbo, Nigeria.
Curr Res Physiol. 2025 Aug 21;8:100162. doi: 10.1016/j.crphys.2025.100162. eCollection 2025.
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/100 g 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.
本研究考察了吗啡对雄性和雌性Wistar大鼠肾功能、抗氧化酶以及炎症和凋亡标志物的影响，同时考虑了性别和剂量依赖性效应。本研究使用了40只Wistar大鼠（20只雄性，20只雌性），每只体重120 - 150克。对照组给予蒸馏水（0.5毫升/100克体重），而实验组每天口服20、40和60毫克/千克的吗啡，持续30天。评估血浆和组织匀浆中的肾功能、炎症和凋亡标志物。将肾脏保存在10%的甲醛生理盐水中用于组织学检查。吗啡显著增加了雄性和雌性大鼠的血浆肌酐水平，且雄性大鼠的增加更为明显。两性的半胱天冬酶-3和肿瘤坏死因子-α也有所升高，但雄性和雌性之间无显著差异。与雌性大鼠相比，雄性大鼠的过氧化氢酶活性显著更高，血浆钠、钾、磷酸盐和氯离子浓度也有所升高。显微照片显示，低剂量和中剂量的吗啡在雄性和雌性大鼠中均导致更严重的肾损伤，导致肾小球萎缩、鲍曼氏间隙增宽以及肾小管刷状缘丧失。相反，高剂量导致的损伤不太明显，只有少数萎缩的肾小球和不清晰的肾小管。与雄性大鼠相比，吗啡在雌性大鼠中诱导了更明显的脂质过氧化和氧化应激，这从它们的血浆电解质和抗氧化酶活性的变化中可以看出。有趣的是，与中剂量和高剂量相比，低剂量导致肾功能、氧化应激和凋亡标志物的变化更为显著。
