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Deltamethrin (DLM) is a synthetic pyrethroid with anti-acaricide and insecticidal properties. It is commonly used in agriculture and veterinary medicine. Humans and animals are exposed to DLM through the ingestion of polluted food and water, resulting in severe health issues. N-acetylcysteine (NAC) is a prodrug of L-cysteine, the precursor to glutathione. It can restore the oxidant-antioxidant balance. Therefore, this research aimed to examine whether NAC may protect broiler chickens against oxidative stress, at the level of biochemical and molecular alterations caused by DLM intoxication. The indicators of liver and kidney injury in the serum of DLM-intoxicated and NAC-treated groups were examined. Furthermore, lipid peroxidation, antioxidant markers, superoxide dismutase activity, and apoptotic gene expressions (caspase-3 and Bcl-2) were investigated. All parameters were significantly altered in the DLM-intoxicated group, suggesting that DLM could induce oxidative damage and apoptosis in hepato-renal tissue. The majority of the changes in the studied parameters were reversed when NAC therapy was used. In conclusion, by virtue of its antioxidant and antiapoptotic properties, NAC enabled the provision of significant protection effects against DLM-induced hepato-renal injury.

Cadmium is a nonessential metal that has heavily polluted the environment due to human activities. It can be absorbed into the human body via the gastrointestinal tract, respiratory tract, and the skin, and can cause chronic damage to the kidneys. The main site where cadmium accumulates and causes damage within the nephrons is the proximal tubule. This accumulation can induce dysfunction of the mitochondrial electron transport chain, leading to electron leakage and production of reactive oxygen species (ROS). Cadmium may also impair the function of NADPH oxidase, resulting in another source of ROS. These ROS together can cause oxidative damage to DNA, proteins, and lipids, triggering epithelial cell death and a decline in kidney function. In this article, we also reviewed evidence that the antioxidant power of plant extracts, herbal medicines, and pharmacological agents could ameliorate cadmium-induced kidney injury. Finally, a model of cadmium-induced kidney injury, centering on the notion that oxidative damage is a unifying mechanism of cadmium renal toxicity, is also presented. Given that cadmium exposure is inevitable, further studies using animal models are warranted for a detailed understanding of the mechanism underlying cadmium induced ROS production, and for the identification of more therapeutic targets.

3-Monochloropropane-1,2-diol (3-MCPD) is a chiral molecule naturally existing as a racemic mixture of (R)- and (S)-enantiomers. It was thoroughly investigated during the 1970s as a male antifertility drug until research was abandoned because of the side effects observed in toxicity studies. More than 20 years later, 3-MCPD, both in the free form and esterified to the fatty acids, was detected in vegetable oil and discovered to be a widespread contaminant in different processed foods. This review summarises the main toxicological studies on 3-MCPD and its esters. Current knowledge shows that the kidney and reproductive system are the primary targets of 3-MCPD toxicity, followed by neurological and immune systems. Despite uncertainties, in vivo studies suggest that renal and reproductive toxicity is mediated by toxic metabolites, leading to inhibition of glycolysis and energy depletion. Few acute, short-term, and subchronic toxicity studies have investigated the 3-MCPD esters. The pattern of toxicity was similar to that of free 3-MCPD. Some evidence suggests that the toxicity of 3-MCPD diesters may be milder than 3-MCPD, likely because of an incomplete enzymatic hydrolysis in the equivalent free form in the gastrointestinal tract. Further research to clarify absorption, metabolism, and long-term toxicity of 3-MCPD esters would be pivotal to improve the risk assessment of these compounds via food.

Ethylene glycol can cause both renal and developmental toxicity, with metabolism playing a key role in the mode of action (MOA) for each form of toxicity. Renal toxicity is ascribed to the terminal metabolite oxalic acid, which precipitates in the kidney in the form of calcium oxalate crystals and is believed to cause physical damage to the renal tubules. The human relevance of the renal toxicity of ethylene glycol is indicated by the similarity between animals and humans of metabolic pathways, the observation of renal oxalate crystals in toxicity studies in experimental animals and human poisonings, and cases of human kidney and bladder stones related to dietary oxalates and oxalate precursors. High-dose gavage exposures to ethylene glycol also cause axial skeletal defects in rodents (but not rabbits), with the intermediary metabolite, glycolic acid, identified as the causative agent. However, the mechanism by which glycolic acid perturbs development has not been investigated sufficiently to develop a plausible hypothesis of mode of action, nor have any cases of ethylene glycol-induced developmental effects been reported in humans. Given this, and the variations in sensitivity between animal species in response, the relevance to humans of ethylene glycol-induced developmental toxicity in animals is unknown at this time.

Doxorubicin (DOX) is a well-known and effective antineoplastic agent of the anthracycline family. But, multiple organ toxicities compromise its invaluable therapeutic usage. Among many toxicity types, nephrotoxicity is one of the major concerns. In recent years many approaches, including bioactive agents of natural origin, have been explored to provide protective effects against chemotherapy-related complications. α-Bisabolol is a naturally occurring monocyclic sesquiterpene alcohol identified in the essential oils of various aromatic plants and possesses a wide range of pharmacological properties such as antioxidant, anti-inflammatory, analgesic, cardioprotective, antibiotic, anti-irritant, and anticancer activities. The present study aimed to evaluate the effects of α-Bisabolol on DOX-induced nephrotoxicity in Wistar male albino rats. Nephrotoxicity was induced in rats by injecting a single dose of DOX (12.5 mg/kg, i.p.), and the test compound, α-Bisabolol (25 mg/kg) was administered intraperitoneally along with DOX as a co-treatment daily for 5 days. DOX-injected rats showed reduction in body weight along with a concomitant fall in antioxidants and increased lipid peroxidation in the kidney. DOX-injection also increased levels/expressions of proinflammatory cytokines namely tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and inflammatory mediators like inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and activated nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinases (MAPK) signaling in the kidney tissues. DOX also triggered apoptotic cell death, evidenced by the increased expression of pro-apoptotic markers like BCL2-Associated X Protein (Bax), cleaved caspase-3, caspase- 9, and cytochrome-C) and a decrease in the expressions of anti-apoptotic markers namely B-cell lymphoma 2 (Bcl2) and B-cell lymphoma-extra large (Bcl-xL) in the kidney. These biochemical alterations were additionally supported by light microscopic findings, which revealed structural alterations in the kidney. However, treatment with α-Bisabolol prevented body weight loss, restored antioxidants, mitigated lipid peroxidation, and inhibited the rise in proinflammatory cytokines, as well as favorably modulated the expressions of NF-κB/MAPK signaling and apoptosis markers in DOX-induced nephrotoxicity. Based on the results observed, it can be concluded that α-Bisabolol has potential to attenuate DOX-induced nephrotoxicity by inhibiting oxidative stress and inflammation mediated activation of NF-κB/MAPK signaling alongwith intrinsic pathway of apoptosis in rats. The study findings are suggestive of protective potential of α-Bisabolol in DOX associated nephrotoxicity and this could be potentially useful in minimizing the adverse effects of DOX and may be a potential agent or adjuvant for renal protection.

New synthetic opioids continue to emerge in the illicit market, and among them, fentanyl analogues pose a serious threat to the public health with their abuse and trafficking. We investigated the toxicity of fentanyl analogues on the liver and kidneys mediated by the µ-opioid receptor (MOR). Our study focused on 4-fluoro-isobutyrylfentanyl (4F-iBF), which is classified as a “narcotic” in Japan; structurally similar analogues 4-chloro-isobutyrylfentanyl (4Cl-iBF) and isobutyrylfentanyl (iBF) were also investigated. Rats that were intraperitoneally administered 4F-iBF (5 mg/kg (12.3 μmol/kg)) or iBF (12.3 μmol/kg) displayed hepatic and renal ischemic-like damage, but 4Cl-iBF (12.3 μmol/kg) did milder renal damage only. We found that the agonist activity of 4F-iBF, at MORs was approximately 7.2 times that of 4Cl-iBF, and that pretreatment with MOR antagonist naltrexone (0.8 mg/kg) alleviated liver and kidney injuries caused by 4F-iBF. These results suggested that 4F-iBF might cause ischemic damage to the liver and kidneys, induced by respiratory depression mediated by MORs. Furthermore, to elucidate the metabolism of fentanyl analogues, we investigated the change over time in the amount of 4F-iBF, 4Cl-iBF, iBF (6.15 μmol/kg, respectively), and their respective metabolites in serum after intraperitoneal administration to rats. The results showed that in 24-h post-dose serum, 4Cl-iBF and iBF were substantially eliminated while 4F-iBF remained at about 30% of the maximum level, and each of the N -dephenylethylated metabolites of 4F-iBF, 4Cl-iBF, and iBF was detected in 2-h post-dose serum. The results from this study revealed information on the hepatic and renal toxicities and metabolism related to fentanyl analogues.

Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major dose-limiting side effects of cisplatin. The aim of this review is to discuss the issue of cisplatin-induced nephrotoxicity in the elderly. Compared with young patients, the incidences of cisplatin-induced nephrotoxicity and acute kidney injury (AKI) in elderly patients are significantly increased, and survival time may be decreased. Following cisplatin treatment of elderly patients, tubulointerstitial injuries will be significantly aggravated based on their original age, both for acute injuries due to cell necrosis and exfoliation and chronic injuries due to interstitial fibrosis, tubular atrophy, and dilatation. The high incidence of cisplatin-induced nephrotoxicity in elderly patients may be associated with renal hypoperfusion; increased comorbidities, such as chronic kidney disease (CKD), cardiovascular disease, and diabetes mellitus; increased use of combined drugs [especially non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitor and angiotensin receptor blockers (ACEI/ARB), and antibiotics]; decreased clearance of cisplatin; and high plasma ultrafilterable cisplatin. Considering hemodynamic stability and water balance, short duration and low volume hydration may be more suitable for treating elderly people. With the increasing popularity of low-dose daily/weekly regimens, we do not recommend routine diuretic treatment for elderly patients. We recommend using a less nephrotoxic platinum if large doses of cisplatin (100mg/m2) are needed.

Cadmium (Cd) is a toxic environmental heavy metal that exerts harmful effects on multiple tissues, including the kidney, liver, lung, and bone, and is also associated with the development of anemia. However, the precise molecular mechanisms underlying Cd-induced toxicity remain incompletely understood. In this paper, we review the recent molecular mechanisms of Cd-induced toxicity and its modification, with a particular emphasis on our recent findings. Using a combination of DNA microarray analysis, protein–DNA binding assays, and siRNA-mediated gene silencing, we identified several transcription factors, YY1, FOXF1, ARNT, and MEF2A, as novel molecular targets of Cd. The downregulation of their downstream genes, including UBE2D2, UBE2D4, BIRC3, and SLC2A4, was directly associated with the expression of cytotoxicity. In addition, PPARδ plays a pivotal role in modulating cellular susceptibility to Cd-induced renal toxicity, potentially by regulating apoptosis-related signaling pathways. In addition to apoptosis pathways, Cd toxicity through ROS generation, ferroptosis and pyroptosis were summarized. Furthermore, it has been revealed that Cd suppresses the expression of iron transport-related genes in duodenal epithelial cells leading to impaired intestinal iron absorption as well as decreased hepatic iron levels. These findings provide a mechanistic basis for Cd-induced iron deficiency anemia, implicating disrupted iron homeostasis as a contributing factor.

Copper nanoparticles are widely utilized in a variety of applications, including metal catalysts, semiconductors, heat transfer fluids in machine tools, and even in antibacterial medications. Forty mature healthy Westar rats were utilized in the current investigation and grouped randomly into four groups ( n = 10 rats/group). Group I (G1) was kept as a control group, but G2, G3, and G4 were intraperitoneally injected with CuO NPs with a dose (5 mg, 10 mg, 25 mg/kg body weight/day) respectively for 9 days. Rats were sacrificed; then, the livers and kidneys were dissected and subjected to histopathological and immunohistochemical examination. Our findings of G2 and G3 revealed mild to moderate degenerative changes within the hepatic parenchyma, moderate blood vessel congestions, glycogen depletion, hemosiderosis, and microvesicular steatosis (fatty changes within the hepatocytes). In addition, at the level of kidney, our examination clarified moderate degenerations of the renal corpuscles and renal tubules with moderate swelling and congestions of the glomerulus with moderate vacuolations in the renal tubules lining epithelium. On the other hand, increasing the dose of CuO NPs, the toxicity became more obvious, where the liver of G4 revealed severe necrosis of hepatocytes with completely disorganizations of the hepatic rays, loss of the hepatic architectures, severe steatosis, severe hemosiderosis, sinusoidal dilatations with congestions, as well as severe fibrous tissue proliferation with anti-inflammatory cell infiltrations specially around portal triad with hyperplasia of bile duct. Meanwhile in kidney, G4 clarified severe necrosis and atrophy of the renal corpuscles with severe damage of Bowman’s capsule leading to completely disorganization and loss of normal renal cortex architectures, severe congestion of the glomerulus, severe necrosis of the renal tubules with damage and sloughing for its lining epithelium, and severe hemorrhage between renal tubules. In addition, severe and diffuse caspase 3 immunoreactivity were observed within the hepatic and renal tissues of G4. The present investigation was concluded that the CuO NPs have a potential toxicological effect on the hepatic and renal tissues that may affect their functions.-->