Acute renal failure (ARF) is a sudden, significant, and often reversible decline in kidney function, with 25% of all hospital-administered pharmaceuticals potentially causing nephrotoxicity. The study investigates the effectiveness of a novel nanoparticle (NP) formulation of glutathione (GSH) and Lepidium sativum (LS) in improving therapeutic outcomes in a rat model of ARF. Sixty adult male albino rats were allocated into ten groups, comprising six rats each, for the study. ARF was created by daily gentamicin (GN) administration for seven consecutive days and various treatment protocols, including chitosan (CS) NPs, spanlastics NPs, as well as conventional, NP formulations of GSH, LS, and their respective combinations. The effect was evaluated through various tests, and properties of nanoparticles were confirmed through characterization processes. The NP compositions markedly enhanced renal function, as seen by reduced urine concentrations of albumin and glucose. Furthermore, the serum concentrations of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C were decreased. Tissue concentrations of nitrite, superoxide dismutase (SOD), and malondialdehyde (MDA), as markers of oxidative stress, were enhanced by both conventional and NP formulations. Additionally, they decreased inflammatory markers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Histological analysis and immunohistochemical testing revealed that the combination therapy, particularly with the nanoforms, significantly decreased caspase 3 cellular immunoexpression, a sign of kidney cellular damage. The findings show that the ARF renal damage is considerably reduced when NPs containing GSH and LS are administered together. The study suggests a promising pharmacological approach for enhancing kidney regeneration and preserving renal function, potentially aiding in new therapeutic interventions for ARF treatment.

Purpose

A multitude of inflammatory cells and chemical mediators initiate a complex cascade that ultimately leads to hepatocyte death and a systemic inflammatory response. This research aimed to investigate the potential effects of sildenafil and neem (Azadirachta indica) extract, in both conventional and nanoparticle (NP) forms, in the treatment of moderate acute liver damage induced by orogastric carbon tetrachloride (CCL₄).

Methods

To induce moderate acute hepatic damage a single oral dosage of CCL₄ (2.5 mL/kg body weight) was provided 24 h before euthanasia. In liver damage-induced CCL₄, sildenafil and neem extract were given in conventional and nanoparticle (PLGA or niosome) forms. To find histological anomalies and hepatic changes, behavioral, biochemical, histopathological, and immunohistochemical methods were used.

Results

The findings indicated that sildenafil and/or neem extract, especially in NP combination, significantly mitigated CCL₄-induced acute moderate liver damage. Indicators of liver function, including aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), albumin, bilirubin and gamma-glutamyl transferase (GGT), shown improvement, particularly with the nanoparticulation of both therapies. Treatment, particularly in NP forms, improved the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase activity (GPx) in liver tissues. A significant reduction in NF-κB expression in hepatic tissue was shown in treatment groups. Also, medication resulted in lower levels of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), caspase-3, and transforming growth factor-beta (TGF-β) in the liver tissue homogenates. Liver function was more significantly improved by the drug-NP combination.

Conclusions

This study verified the beneficial therapeutic effects of the combination of sildenafil and neem extract, particularly in NP forms, using biochemical, histological, and immunohistochemical analyses in a rat model of liver damage.