Background: Gentamicin (GM) is extensively used as an antibiotic for the treatment of infections caused by Gram-negative bacteria. Oxidative stress and proinflammatory cytokines are implicated in GM-induced renal damage. Chrysin (CH), also known as 5,7-dihydroxyflavone, has been used in traditional medicine to treat various kidney disorders. The aim of this study was to investigate the antioxidant, anti-apoptotic, and anti-inflammatory effects of CH against nephrotoxicity induced by GM. Methods: Male rats were separated into four equal groups: a negative control group (NC), a CH-treated group (100 mg/kg/day per os), a group treated with GM (100 mg/kg/day IM), and a group treated with both GM and CH (100 mg/kg/day), for 10 days. Blood and urine renal markers were investigated. Results: GM caused increases in the serum creatinine and urea levels and decreases in creatinine clearance, urine flow, and urine volume in the GM-treated rats. Moreover, there were increases in the levels of IL-1β, TNF-α, IL-18, and MDA in the renal tissues, with an augmented expression of NF-κB/KIM-1, as well as decreases in antioxidant marker (GSH, GPx, CAT, and SOD) activities and decreased expressions of the anti-inflammatory transcription factors Nrf2 and AKT. The simultaneous treatment with CH in the GM-treated group protected renal tissues against the nephrotoxicity induced by GM, as demonstrated by the normalization of renal markers and improvement in histopathological damage. Conclusions: This study reveals that CH may attenuate GM-induced renal toxicity in rats.

Hazardous heavy metals, particularly cadmium (Cd), are widely distributed in the environment and cause oxidative stress in various animal and human organs. Clove oil (CLO), a common aromatic spice, has been used as a traditional medication as it has potent anti-inflammatory, antioxidant, and hepatoprotective properties. Background/Objectives: This study aimed to investigate the antioxidant, antiapoptotic, and anti-inflammatory effects of clove oil (CLO) against hepatorenal toxicity induced by cadmium (Cd). Methods: Twenty rats were equally divided into four groups: a control group, a Cd group treated with 15 mg/kg b.wt CdCl₂, a CLO group administered 200 mg/kg b.wt CLO, and a Cd+CLO group. All groups were orally treated for 4 weeks. Results: Cadmium (Cd) exposure caused anemia and hepatorenal damage, as evidenced by increased serum levels of urea, creatinine, uric acid, total bilirubin (including its direct and indirect fractions), and elevated activities of liver enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). However, total protein and albumin levels decreased. Furthermore, there was a decrease in the levels of glutathione, glutathione transferase, and catalase in the liver antioxidant profiles. Meanwhile, malondialdehyde levels increased. Cadmium toxicity caused elevated expression of liver apoptosis markers, such as tumor necrosis factor-alpha (TNF-α) and caspase-3, and inflammation. CLO ameliorated the oxidative effects of Cd through decreasing urea (27.4%), creatinine (41.6%), liver enzymes, and hepatic apoptotic markers while increasing levels of total protein, albumin, and hepatic values of SOD (60.37%), CAT (64.49%), GSH (50.41%), and GST (9.16%). Conclusions: Hematological and biochemical parameters, as well as the antioxidant system, improved following clove oil treatment, leading to a reduction in hepatorenal damage. Therefore, it is possible to conclude that CLO protects rats from inflammation, apoptosis, and hepatorenal oxidative damage caused by Cd poisoning. Comprehensive translational research is required to validate CLO’s efficacy and safety of use in humans. Future studies should focus on elucidating the precise molecular mechanisms, optimal dosing strategies, and potential synergistic effects of CLO with other therapeutic agents.

Our study intended to explore Hesp antioxidant and anti-inflammatory effects against TAA hepatic fibrosis in rats. Hesperidin (Hesp), is a pharmacologically active flavonoid, found abundantly in citrus species. Our present research attempts to inspect the potential hepatoprotective role of Hesp against thioacetamide (TAA)-induced hepatic fibrosis. Thirty-two male albino rats were split up into four equal groups, each with eight rats: Cont group was treated with ip saline. Every other day, the TAA group was injected 100 mg/kg BW ip TAA, Hesp group received every day oral Hesp 200 mg/kg BW as well as TAA + Hesp group received both therapies (TAA, Hesp) for eight successive weeks. Hesp in TAA treated group reduces ALT, AST, and ALP activities, total, direct bilirubin, total cholesterol, and triglycerides, meanwhile TP, Alb, globulin, A/G ratio levels were insignificantly differed. The antioxidant capacity of Hesp was pronounced by a marked reduction in MDA level. While the antioxidant markers (SOD, CAT, GSH) were insignificantly changed after Hesp treatment. A strong significant correlation in treated rats between fibrosis score and CD34 and FGF23 gene expression. Liver sections from dual-treated rats showed a moderately decreased hepatic lesion and the dense, bluish-stained fibrous tissue by Masson’s trichrome. Elevated gene expressions of CD34 and FGF23 after TAA hepatotoxicity were diminished by the antifibrotic effect of Hesp. Also, immunohistochemical expression showed reduction of TGF-β and α-SMA in hepatocytes in the dual therapy group. Hesp possesses a potent antioxidant, and antifibrotic activities against TAA induced hepatic fibrosis by modulating TGF-β/α-SMA pathways.

Background and Objectives: 5-Fluorouracil (5-FU) is a widely prescribed and effective chemotherapeutic drug, but its cardiotoxic side effects pose a significant challenge to its use. Identifying a protective agent that does not affect its anticancer efficacy is essential. Our study aimed to investigate the cardioprotective effect of N-acetyl cysteine (NAC) against 5-FU-induced cardiac injury and to elucidate the underlying mechanisms. Materials and Methods: This study included four experimental groups, each with eight rats (n = 8): Group I (control group), Group II (NAC group), Group III (5-FU group), and Group IV (combined group 5-FU+NAC). Cardiac enzymes, oxidative stress, inflammatory, and apoptotic markers were investigated, and cardiac sections from the different groups were histologically examined. Results: Co-treatment of 5-FU with NAC resulted in significantly lower levels of cardiac enzymes (alanine transaminase (ALT) by 62.1%, aspartate transaminase (AST) by 73.6%, lactate dehydrogenase (LDH) by 55.8%, and creatine kinase (CK) by 57.3%) compared to the 5-FU group, along with marked improvements in heart tissue histology. Additionally, NAC enhanced the activity of cardiac antioxidant enzymes (superoxide dismutase (SOD) by 295.6%, catalase (CAT) by 181%, and glutathione peroxidase (GPx) by 320.9%) while decreasing malondialdehyde (MDA) by 51.1%, a marker of membranous lipid peroxidation. This might be due to significant upregulation of the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway at the gene and protein levels. The combined treatment significantly decreased the gene expression of the toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) pathway. Furthermore, it downregulated the protein levels of inflammatory markers, including tumor necrosis factor-alpha (TNF-α) by 29.9%, interleukin-1 beta (IL-1β) by 21.9%, and interleukin-6 (IL-6) by 49.3%. Moreover, it upregulated the antiapoptotic marker B-cell lymphoma 2 (Bcl-2) protein levels by 269% and decreased apoptotic indicators Bcl-2-associated protein x (Bax) by 57.9% and caspase-3 by 30.6% compared to the 5-FU group. Conclusions: This study confirmed that NAC prevented the cardiotoxic effect of 5-FU through its antioxidant, anti-inflammatory, and antiapoptotic properties, suggesting its potential application as an adjuvant therapy in chemotherapy to alleviate 5-FU-induced cardiotoxicity.

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a growing global health burden, yet no approved pharmacological therapy currently exists. Purpose: The purpose of this study is to investigate the prophylactic and therapeutic potential of Rebamipide, a mucosal-protective and anti-inflammatory drug, in a high-fat diet (MHFD)-induced MASLD rat model, integrating quantitative liver proteomics, network analysis, and histopathology. Methods: Male Wistar rats were fed MHFD for 16 weeks and treated with Rebamipide either prophylactically (Reb T1, co-administered with diet) or therapeutically (Reb T2, administered post-NASH onset). Label-free LC-MS/MS proteomics combined with principal component analysis (PCA), partial squares discriminant analysis (PLS-DA), and enrichment analyses (including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome via g: Profiler, network mapping, and Rat Genome Database (RGD) mining) revealed that MHFD had the following impacts: it induced the profound suppression of mitochondrial chaperones (Hspa9), microsomal triglyceride transfer protein (Mttp), and cytochrome P450 isoforms (Cyp2c6); it disrupted lipid trafficking, oxidative stress defense, and xenobiotic metabolism. Results: Rebamipide prophylaxis preserved lipid-handling proteins, prevented glycogen loss, and maintained antioxidant defenses. In contrast, therapeutic administration reversed established steatosis and remodeled metabolic pathways, enhancing fatty acid β-oxidation, detoxification, and mitochondrial protein import. Nine shared proteins across all comparisons, including MTTP and multiple Stress-70 mitochondrial isoforms, mapped to three core genes (Mttp, Cyp2c6, Hspa9) central to lipid transport, protein import, and metabolic stress adaptation. KEGG and Reactome analyses highlighted Rebamipide’s modulation of bile acid synthesis, ceramide and phosphatidylcholine metabolism, lipoprotein remodeling, and MAPK signaling. Histopathological evaluation confirmed Rebamipide’s efficacy, showing reduced steatosis and the normalization of the hepatocyte structure, with near-complete restoration in the therapeutic (Reb T2) group compared to partial protection in the Reb T1 group. Conclusions: These findings demonstrate Rebamipide’s dual-phase, multi-targeted mechanism: early protection against diet-induced metabolic injury and robust reversal of established MASLD pathology. The identified protein triad (Mttp, Cyp2c6, Hspa9) and associated pathways provide novel biomarker candidates and mechanistic insight supporting Rebamipide’s repurposing as a therapeutic for metabolic liver disease.