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.

Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague–Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1β), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity.

Chlorfenapyr (CFP) is a widely used pesticide associated with nephrotoxicity through oxidative stress, inflammation, and mitochondrial dysfunction. This study investigated the protective effects of limonene (LM) and its nano-liposomal formulation (LM-LNPs) against CFP-induced renal injury in rats. Animals were divided into six groups—control, LM, LM-LNPs, CFP, CFP + LM, and CFP + LM-LNPs—and treated orally for 30 days. CFP exposure resulted in marked renal dysfunction, histopathological and ultrastructural damage, suppression of the NRF2/HO-1/NQO1 antioxidant pathway, depletion of endogenous antioxidants excessive generation of reactive oxygen and nitrogen species, lipid peroxidation products, and DNA damage. These changes were accompanied by activation of NF-κB/COX-2-mediated inflammation, mitochondrial respiratory impairment, disrupted energy metabolism, and induction of apoptosis. Co-treatment with LM significantly ameliorated these alterations, whereas LM-LNPs produced greater improvements in renal function, tissue architecture, redox homeostasis, mitochondrial function, and inflammatory and apoptotic signaling. Immunohistochemical analyses further confirmed enhanced NRF2 expression and reduced NF-κB immunoreactivity in LM-LNP-treated kidneys. Overall, nano-liposomal delivery enhanced the renoprotective efficacy of limonene, highlighting its potential as a therapeutic strategy against pesticide-induced kidney injury.