Retinoic acid reduces kidney injury by regulating oxidative stress, NRF-2, and apoptosis in hyperoxic mice

Abstract

Nuclear factor-erythroid-2-related factor-2 (NRF-2) is a cellular resistance protein to oxidants. We investigated the effect of exogenous all-trans retinoic acid (ATRA) on the antioxidant system and NRF-2 in mice kidneys under hyperoxia-induced oxidative stress. Mice were divided into four groups. Daily, two groups were given either peanut-oil/dimethyl sulfoxide (PoDMSO) mixture or 50 mg/kg ATRA. Oxidative stress was induced by hyperoxia in the remaining groups. They were treated with PoDMSO or ATRA as described above, following hyperoxia (100% oxygen) for 72 h. NRF-2 and active-caspase-3 levels, lipid peroxidation (LPO), activities of antioxidant enzymes, xanthine oxidase (XO), paraoxonase1 (PON1), lactate dehydrogenase (LDH), tissue factor (TF), and prolidase were assayed in kidneys. Hyperoxia causes kidney damage induced by oxidative stress and apoptosis. Increased LPO, LDH, TF, and XO activities and decreased PON1 and prolidase activities contributed to kidney damage in hyperoxic mice. After hyperoxia, increases in the activities of antioxidant enzymes and NRF-2 level could not prevent this damage. ATRA attenuated damage via its oxidative stress-lowering effect. The decreased LDH and TF activities increased PON1 and prolidase activities, and normalized antioxidant statuses are indicators of the positive effects of ATRA. We recommend that ATRA can be used as a renoprotective agent against oxidative stress induced-kidney damage. This study investigates the protective effects of all-trans retinoic acid (ATRA) against oxidative stress and oxidative stress-induced tissue damage in mouse kidneys. Exposure to high oxygen levels significantly damages kidney tissues by increasing lipid peroxidation and enzyme activities, leading to cellular dysfunction. However, treatment with ATRA demonstrated a remarkable ability to attenuate these effects, increase the activity of antioxidant defenses, and stabilize essential renal enzymes. These findings suggest that ATRA may be a potent renoprotector and offer a promising approach to managing oxidative stress-induced renal damage.