Doxorubicin (DOX) is a frequent chemotherapeutic drug used to treat various malignant tumors. One of the key factors that diminish its therapeutic importance is DOX-induced nephrotoxicity. The first-line oral antidiabetic drug is metformin (Met), which also has antioxidant properties. The purpose of our study was to investigate the underlying molecular mechanisms for the potential protective effects of Met on DOX-triggered nephrotoxicity. Four animal groups were assigned as follows; animals received vehicle (control group), 200 mg/kg Met (Met group), DOX 15 mg/kg DOX (DOX group), and a combination of DOX and Met (DOX/Met group). Our results demonstrated that DOX administration caused marked histological alterations of widespread inflammation and tubular degeneration. Notably, the DOX-induced dramatic up-regulation of the nuclear factor-kappa B/P65 (NF-κB/P65), microtubule-associated protein light chain 3B (LC3B), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-1beta (IL-1β), 8-hydroxy-2′ -deoxyguanosine (8-OHdG), and Beclin-1 in renal tissue. A marked increase in the malondialdehyde (MDA) tissue level and a decrease in the total antioxidant capacity (TAC) were also recorded in DOX-exposed animals. Interestingly, Met could minimize all histopathological changes as well as the disruptions caused by DOX in the aforementioned measures. Thus, Met provided a workable method for suppressing the nephrotoxicity that occurred during the DOX regimen via the deactivation of the Beclin-1/LC3B pathway.

Concerns regarding the possible hazards to human health have been raised by the growing usage of silica nanoparticles (SiNPs) in a variety of applications, including industrial, agricultural, and medical applications. This in vivo subchronic study was conducted to assess the following: (1) the toxicity of orally administered SiNPs on the liver, kidneys, and adrenal glands; (2) the relationship between SiNPs exposure and oxidative stress; and (3) the role of magnesium in mitigating these toxic effects. A total of 24 Sprague Dawley male adult rats were divided equally into four groups, as follows: control group, magnesium (Mg) group (50 mg/kg/d), SiNPs group (100 mg/kg/d), and SiNPs+ Mg group. Rats were treated with SiNPs by oral gavage for 90 days. The liver transaminases, serum creatinine, and cortisol levels were evaluated. The tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured. Additionally, the weight of the organs and the histopathological changes were examined. Our results demonstrated that SiNPs exposure caused increased weight in the kidneys and adrenal glands. Exposure to SiNPs was also associated with significant alterations in liver transaminases, serum creatinine, cortisol, MDA, and GSH. Additionally, histopathological changes were significantly reported in the liver, kidneys, and adrenal glands of SiNPs-treated rats. Notably, when we compared the control group with the treated groups with SiNPs and Mg, the results revealed that magnesium could mitigate SiNPs-induced biochemical and histopathologic changes, confirming its effective role as an antioxidant that reduced the accumulation of SiNPs in tissues, and that it returns the levels of liver transaminases, serum creatinine, cortisol, MDA, and GSH to almost normal values.