Naringenin (NRG) is one of the most important naturally occurring flavonoids, predominantly found in some edible fruits, such as citrus species and tomatoes. It has several biological activities, such as antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic, and cardioprotective effects. The heavy metal lead is toxic and triggers oxidative stress, which causes toxicity in many organs, including the liver and brain. This study explored the potential protective role of NRG in hepato- and neurotoxicity caused by lead acetate in rats. Four groups of ten male albino rats were included: group 1 was a control, group 2 was orally treated with lead acetate (LA) at a dose of 500 mg/kg BW, group 3 was treated with naringenin (NRG) at a dose of 50 mg/kg BW, and group 4 was treated with 500 mg/kg LA and 50 mg/kg NRG for 4 weeks. Then, blood was taken, the rats were euthanized, and liver and brain tissues were collected. The findings revealed that LA exposure induced hepatotoxicity with a significant increase in liver function markers (p < 0.05). In addition, albumin and total protein (TP) and the albumin/globulin ratio (A/G ratio) (p < 0.05) were markedly lowered, whereas the serum globulin level (p > 0.05) was unaltered. LA also induced oxidative damage, demonstrated by a significant increase in malonaldehyde (MDA) (p < 0.05), together with a pronounced antioxidant system reduction (SOD, CAT, and GSH) (p < 0.05) in both liver and brain tissues. Inflammation of the liver and brain caused by LA was indicated by increased levels of nuclear factor kappa beta (NF-κβ) and caspase-3, (p < 0.05), and the levels of B-cell lymphocyte-2 (BCL-2) and interleukin-10 (IL-10) (p < 0.05) were decreased. Brain tissue damage induced by LA toxicity was demonstrated by the downregulation of the neurotransmitters norepinephrine (NE), dopamine (DA), serotonin (5-HT), and creatine kinase (CK-BB) (p < 0.05). Additionally, the liver and brain of LA-treated rats displayed notable histopathological damage. In conclusion, NRG has potential hepato- and neuroprotective effects against lead acetate toxicity. However, additional research is needed in order to propose naringenin as a potential protective agent against renal and cardiac toxicity mediated by lead acetate.

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.

Vitamin D₃ (VD₃) is a sunshine hormone that regulates cellular proliferation, differentiation, apoptosis, and angiogenesis related to liver parenchyma. We used a thioacetamide (TAA)-induced hepatic fibrosis rat model in our study to investigate the beneficial roles of VD₃ to overcome extensive liver fibrosis. Randomly, four equal groups (eight rats per group) underwent therapy for eight successive weeks: a control group, a group treated with TAA 100 mg/kg BW IP every other day, a group treated with VD₃ 1000 IU/kg BW IM every day, and a TAA+VD group treated with both therapies. Treatment with VD₃ after TAA-induced hepatic fibrosis was found to alleviate elevated liver function measures by decreasing ALT, AST, and ALP activity; decreasing total bilirubin, direct bilirubin, cholesterol, and triglyceride levels; and increasing glucose and 25[OH]D₃. Rats treated with VD₃ showed marked decreases in MDA and increased SOD, CAT, and GSH levels. In addition, CD34 and FGF23 gene expressions were reduced after dual therapy. Liver sections from the TAA+VD group showed markedly decreased hepatic lesions, and Masson’s trichrome stain showed a marked decrease in dense bluish-stained fibrous tissue. The immunohistochemical expression of TGF-β and α-SMA showed markedly decreased positive brown cytoplasmic expression in a few hepatocytes, clarifying the antifibrotic effect of VD₃ in hepatic fibrosis. In conclusion, VD₃ alleviates hepatotoxicity and fibrosis caused by TAA.

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.

The present study investigated the protective effects of edaravone (EDA), metformin (Met), and their combined treatment against diabetic nephropathy (DN) in rats. Sixteen normal non-diabetic rats were allocated to the negative control (NC) and EDA-treated control (EDA10; 10 mg/kg/day) groups and received a standard diet throughout the study. Type 2 diabetes was induced by feeding male Wistar rats (n = 40) a high-fat diet (HFD) for four weeks followed by a single intraperitoneal injection of streptozotocin (STZ; 40 mg/kg). Of the 40 rats, 36 developed diabetes; 32 were subsequently maintained on the HFD for an additional four weeks to establish DN and were then randomly allocated into four equal diabetic groups (n = 8/group) for the 8-week therapeutic intervention as follows: untreated DN, DN treated with Met alone (300 mg/kg/day), and DN treated with Met combined with either 5 or 10 mg/kg/day EDA. The diabetic animals remained on the HFD throughout the intervention period. Blood, urine, and renal tissue were collected to assess glucose homeostasis along with renal function, histopathology, oxidative stress, antioxidant defense, inflammation, apoptosis, and selected molecular regulatory markers at both gene and protein levels. DN was associated with impaired glucose homeostasis together with marked renal dysfunction, histopathological injury, oxidative stress, inflammation, and apoptosis. While Met significantly ameliorated many of these abnormalities, co-administration of EDA produced additional improvements, with the greatest overall effects observed with the higher EDA dose. Correlation and Mantel network analyses showed stronger associations of Mapk1 expression with renal injury, inflammation, and oxidative stress markers in DN, whereas combined treatment was associated with stronger relationships between Akt1 and Hmox1 expression and the cytoprotective biomarkers. In conclusion, combined EDA and Met treatment produced greater overall renoprotective effects than Met monotherapy, with the higher EDA dose showing the strongest nephroprotection. Further studies are required to determine the mechanisms underlying EDA-associated renoprotection and their translational relevance in humans.