L-arginine and lisinopril supplementation protect against sodium fluoride-induced nephrotoxicity and hypertension by suppressing mineralocorticoid receptor and angiotensin-converting enzyme 3 activity

Abstract

Sodium fluoride (NaF) is one of the neglected environmental toxicants that has continued to silently cause toxicity to both humans and animals. NaF is universally present in water, soil and the atmosphere. The persistent and alarming rate of increase in cardiovascular and renal diseases and disorders caused by chemicals such as sodium fluoride (NaF) in mammalian tissues have led to the use of various drugs for the treatment of these diseases. This study aims at evaluating the renoprotective and antihypertensive effects of L- Arginine on NaF-induced nephrotoxicity. Thirty male Wistar rats (150–180 g) were used in this study. The rats were randomly divided into five groups of six rats each as Control, NaF (300 ppm), NaF + L- Arginine (100 mg/kg), NaF + L- Arginine (200 mg/kg), and NaF + Lisinopril (10 mg/kg), respectively; orally for eight days. Histopathological examination and immunohistochemistry of renal angiotensin converting enzyme (ACE) and mineralocorticoid receptor (MCR) were performed. Markers of renal damage, oxidative stress, antioxidant defence system, and blood pressure parameters were determined. L- Arginine significantly (p < 0.05) ameliorated the hypertensive effects of NaF. The systolic, diastolic and mean arterial blood pressure of the treated groups were significantly (p < 0.05) reduced compared with the hypertensive group. This finding was concurrent with significantly increased serum bioavailability of nitric oxide in the hypertensive treated groups. Also, there was significant reduction in the level of blood urea nitrogen (BUN) and creatinine in the serum of the hypertensive rats treated with L- arginine. There was significant (p < 0.05) reduction in markers of oxidative stress such as hydrogen peroxide (H2O2), malondialdehyde (MDA) and protein carbonyl (PCO) and concurrent increase in the levels of antioxidant enzymes in the kidney of hypertensive rats treated with L- arginine. The results of this study suggest that L- Arginine normalized high blood pressure, reduced oxidative stress, reduced the expression of renal ACE and MCR, and improved nitric oxide production. Thus, L- Arginine holds promise as a potential therapy against hypertension and renal damage.