Therapeutic Potential of Methylindoline Derivative in Ameliorating Cadmium-Induced Nephritis Experimented in Zebrafish Model

Abstract

Since kidney diseases are a major global concern, their impact on public health makes them an important area of study. The kidneys, as the primary organs responsible for excreting waste, are particularly vulnerable to heavy metal poisoning. Cadmium (Cd), a naturally occurring heavy metal found in contaminated food and water, poses a serious risk to renal health. Due to their remarkable biological properties, methylindoline derivatives are being investigated for a variety of medicinal applications. The primary objective of this study is to screen and assess the anti-inflammatory and anti-nephritic qualities of methylindoline derivatives (IA, IB, IC, ID, IE). Through network pharmacology and molecular docking analyzes, the derivative IC ((E)-3-(2-(4-methoxyphenyl)-2-oxoethylidene)-5-methylindolin-2-one) was identified for further study. In In Vitro screening, IC showed strong antioxidant and anti-inflammatory properties in a dose-dependent manner. It effectively reduced oxidative stress, lipid peroxidation, and apoptosis induced by cadmium in zebrafish. In renal tissues, IC treatment decreased levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA) while restoring the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). The expression of pro-inflammatory cytokine genes, including TNF-α, IL-1β, IL-6, and NF-κB, was also significantly downregulated by IC. Histopathological analysis of zebrafish kidneys demonstrated the restoration of renal tissue architecture, validating the protective effects of IC. These results highlight IC's therapeutic potential in treating cadmium-induced nephritis.