Aflatoxin B₁ (AF) is an unavoidable environmental pollutant that contaminates food, feed, and grains, which seriously threatens human and animal health. Arabic gum (AG) has recently evoked much attention owing to its promising therapeutic potential. Thus, the current study was conducted to look into the possible mechanisms beyond the ameliorative activity of AG against AF-inflicted hepatic injury. Male Wistar rats were assigned into four groups: Control, AG (7.5 g/kg b.w/day, orally), AF (200 µg/kg b.w), and AG plus AF group. AF induced marked liver damage expounded by considerable changes in biochemical profile and histological architecture. The oxidative stress stimulated by AF boosted the production of plasma malondialdehyde (MDA) level along with decreases in the total antioxidant capacity (TAC) level and glutathione peroxidase (GPx) activity. Additionally, AF exposure was associated with down-regulation of the nuclear factor erythroid2–related factor2 (Nrf2) and superoxide dismutase1 (SOD1) protein expression in liver tissue. Apoptotic cascade has also been evoked following AF-exposure, as depicted in overexpression of cytochrome c (Cyto c), cleaved Caspase3 (Cl. Casp3), along with enhanced up-regulation of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, inducible nitric oxide synthase (iNOS), and nuclear factor kappa-B transcription factor/p65 (NF-κB/p65) mRNA expression levels. Interestingly, the antioxidant and anti-inflammatory contents of AG may reverse the induced oxidative damage, inflammation, and apoptosis in AF-exposed animals.

Although the combination of antibiotics is generally well-tolerated, they may have nephrotoxic effects. This study investigated whether tigecycline (TG) and gentamicin (GM) co-administration could accelerate renal damage. Male Wistar rats were randomly divided into six experimental groups: the control, TG7 (tigecycline, 7 mg/kg), TG14 (tigecycline, 14 mg/kg), GM (gentamicin, 80 mg/kg), TG7+GM, and TG14+GM groups. The combination of TG and GM evoked renal damage seen by the disruption of kidney function tests. The perturbation of renal tissue was mainly confounded to the TG and GM-induced oxidative damage, which was exhibited by marked increases in renal MDA (malondialdehyde) along with a drastic reduction in GSH (reduced-glutathione) content and CAT (catalase) activity compared to their individual treatments. More obvious apoptotic events and inflammation were also revealed by elevating the annexin-V and interleukin-6 (IL-6) levels, aside from the upregulation of renal PCNA (proliferating cell nuclear antigen) expression in the TG and GM concurrent treatment. The principal component analysis indicated that creatinine, urea, annexin-V, IL-6, and MDA all played a role in discriminating the TG and GM combined toxicity. Oxidative stress, inflammatory response, and apoptosis were the key mechanisms involved in this potentiated toxicity.

Melamine (ML), a chemical substance of high nitrogen content, is used as a food adulterant. Former evidences implied that ML could induce a variety of toxic effects including neurotoxicity and cognitive impairment. Therefore, the aim of this study was to delineate the protective effect of the nootkatone (NK) against ML-induced neural adverse effects. Rats were orally pretreated with NK (5 and 10 mg/kg) prior to the oral administration of ML (700 mg/kg) for a period of 28 days. Our findings unveiled remarkable alleviating effect of NK on MK-induced neurobehavioral disturbance in open field test. Furthermore, NK lessened ML-caused increases in the acetylcholine esterase level in the brain tissue of exposed rats. NK also decreased the neural oxidative stress as represented by elevated levels of SOD, CAT, and GSH along with decreased MDA and NO levels. Upregulated mRNA expression levels of neural NRF-2 and HO-1 were noticed after NK administration. Remarkable anti-inflammatory impact was prominent by decreased neural IL-1β, and TNF-α along with downregulated NF-κB and TLR-4 gene expression levels in NK-treated rats. Noteworthily, pre-treatment with NK decreased the immune reaction of RAGE and HMGB-1 induced by oral ML exposure. Brain histological examination validated the obtained biochemical and molecular results. To sum up, these outcomes reveal that NK successfully alleviated the neural damage induced by ML via blocking of oxidative stress, and inflammatory signaling pathways. Consequently, our study may suggest NK as a new effective therapeutic supplement for treatment of ML-mediated neurotoxicity in rats via inhibition of HMGB-1-RAGE/TLR-4/NF-κB.

Background and Objectives: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world. Due to failure of the traditional drugs to produce a complete cure for AD, the search for new safe and effective lines of therapy has attracted the attention of ongoing research. Canagliflozin is an anti-diabetic agent with proven efficacy in the treatment of neurological disorders in which mitochondrial dysfunction, oxidative stress, apoptosis, and autophagy play a pathophysiological role. Elucidation of the potential effects of different doses of canagliflozin on AD induced by aluminium chloride in rats and exploration of the molecular mechanisms that may contribute to these effects were the primary objectives of the current study. Materials and Methods: In a rat model of AD, the effect of three different doses of canagliflozin on the behavioural, biochemical, and histopathological alterations induced by aluminium chloride was assessed. Results: Canagliflozin administered to aluminium chloride-treated animals induced dose-dependent normalisation in the behavioural tests, augmentation of the antioxidant defence mechanisms, inhibition of TXNIP/NLRP3 inflammasome signalling, modulation of the SIRT1/HMGB1 axis, interference with the pro-inflammatory and the pro-apoptotic mechanisms, and restoration of the mitochondrial functions and autophagy in the hippocampal tissues to approximately baseline values. In addition, canagliflozin exhibited an interesting dose-dependent ability to repress aluminium chloride-induced histopathological changes in the brain. Conclusions: The effects of canagliflozin on oxidative stress, mitochondrial functions, inflammatory pathways, and autophagy signals may open new gates towards the mitigation of the pathologic features of AD.

Melamine (ML) is a common environmental contaminant, commonly used in food fraud, representing a serious health hazard and jeopardizing human and animal health. Recently, nootkatone (NK), a naturally occurring sesquiterpenoid, has garnered considerable attention due to its potential therapeutic advantages. We investigated the potential mechanisms underlying the protective effects of NK against ML-induced liver injury in rats. Five groups were utilized: control, ML, NK10, ML-NK5, and ML-NK10. ML induced substantial hepatotoxicity, including considerable alterations in biochemical parameters and histology. The oxidative distress triggered by ML increased the generation of malondialdehyde (MDA) and nitric oxide (NO) and decreased levels of reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. In addition, decreased expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and increased nuclear factor kappa beta (NF-κB) expression levels were observed in hepatocytes, which indicated the occurrence of inflammatory changes following ML exposure. These alterations were alleviated by NK supplementation in a dose-dependent manner. The data revealed that the favorable effects of NK were attributed, at least in part, to its antioxidant and anti-inflammatory properties. Moreover, our results were supported by molecular docking studies that revealed a good fit and interactions between NK and antioxidant enzymes. Thus, the current study demonstrated that NK is a potential new food additive for the prevention or treatment of ML-induced toxicity.