Abstract
Acetaminophen (APAP) is the most commonly used nonprescription antipyretic-analgesic drug. This medication is thought to be safe at the suggested dosage (4 g/24 h), but its overdose (up to 2.5 g/kg) can cause severe injuries to the human body, including renal injury. APAP has various toxic effects on nephrons, as it leads to an excessive free radical generation that, in turn, results in a disturbance in the redox homeostasis of cells, causing oxidative stress. To replenish this oxidative stress, there is an ultimate urge for natural therapies that can retain the cellular homeostasis of nephrons by diminishing the overdose impression of acetaminophen. The principle objective of this work is to appraise nephrotoxicity due to APAP and its amelioration through the antioxidant properties of aqueous extracts of selected medicinal plants: Urtica dioica, Capsella bursa-pastoris, and Inula racemosa (UD, CBP, and IR, respectively). The pH stability of the nutraceuticals used was examined by determining the impact of pH 4, pH 7 and pH 9 on the DPPH radical scavenging activity of aqueous plant extracts. Gas chromatography-Mass spectroscopy (GC-MS) analytical technique was performed to determine the volatile organic phytochemical profiles of all three medicinal plants. Male Swiss albino mice were used for the present investigation. The animals were distributed into five groups of (n = 6), a total of 30 mice, for in vivo analysis. Group 1 served as the control group; group 2 received a single IP dose of APAP (600 mg/kg); group 3 received APAP pretreated with UD (300 mg/kg); group 4 received APAP pretreated with CBP (300 mg/kg); and group 5 received APAP pretreated with IR (300 mg/kg). Overdose of the APAP- induced a significant (p < 0.05) alterations in the total protein concentration, weight and the nephrological architecture in renal tissue, as observed through biochemical assays and histopathological examinations. Due to nephrotoxicity, there was a substantial (p < 0.05) drop in body weight and total protein contents in the APAP alone group when compared to the treatment groups. There was remarkable protection against APAP-induced alterations in the total protein of renal homogenate in the treatment groups. Histopathological analysis (H&E staining) of the mice kidneys indicated severe deterioration in the APAP alone group, whereas the therapy groups showed considerable nephroprotection towards APAP-induced abnormalities. The biochemical findings and histopathological study of the kidneys revealed that the herbal extracts (UD, CBP, and IR) have a nephroprotective potential against APAP-induced nephropathy. The trend of efficacy was observed as UD > CBP > IR. However, extensive study is needed to determine the likely ameliorative mechanism of these nutraceuticals.