This study investigates the effects of bisphenol A (BPA) contamination on the kidney and the possible protection by melatonin in experimental rats and isolated mitochondrial models. Rats exposed to BPA (50, 100, and 150 mg/kg, i.p.) for 5 weeks demonstrated renal damages as evident by increased serum urea and creatinine and decreased creatinine clearance, together with the presence of proteinuria and glomerular injuries in a dose‐dependent manner. These changes were associated with increased lipid peroxidation and decreased antioxidant glutathione and superoxide dismutase. Mitochondrial dysfunction was also evident as indicated by increased reactive oxygen species production, decreased membrane potential change, and mitochondrial swelling. Coadministration of melatonin resulted in the reversal of all the changes caused by BPA. Studies using isolated mitochondria showed that BPA incubation produced dose‐dependent impairment in mitochondrial function. Preincubation with melatonin was able to sustain mitochondrial function and architecture and decreases oxidative stress upon exposure to BPA. The findings indicated that BPA is capable of acting directly on the kidney mitochondria, causing mitochondrial oxidative stress, dysfunction, and subsequently, leading to whole organ damage. Emerging evidence further suggests the protective benefits of melatonin against BPA nephrotoxicity, which may be mediated, in part, by its ability to diminish oxidative stress and maintain redox equilibrium within the mitochondria.

Diabetic nephropathy (DN) is the primary cause of end-stage renal disease worldwide. Oxidative stress and mitochondrial dysfunction are central to its pathogenesis. Rice husk, the leftover from the milling process, is a good source of phytochemicals with antioxidant activity. This study evaluated the possible protection of purple rice husk extract (PRHE) against diabetic kidney injury. Type 2 diabetic rats were given vehicle, PRHE, metformin, and PRHE+metformin, respectively, while nondiabetic rats received vehicle. After 12 weeks, diabetic rats developed nephropathy as proven by metabolic alterations (increased blood glucose, insulin, HOMA-IR, triglycerides, cholesterol) and renal abnormalities (podocyte injury, microalbuminuria, increased serum creatinine, decreased creatinine clearance). Treatment with PRHE, metformin, or combination diminished these changes, improved mitochondrial function (decreased mitochondrial swelling, reactive oxygen species production, membrane potential changes), and reduced renal oxidative damage (decreased lipid peroxidation and increased antioxidants). Increased expression of PGC-1α, SIRT3, and SOD2 and decreased expression of Ac-SOD2 correlated with the beneficial outcomes. HPLC revealed protocatechuic acid and cyanidin-3-glucoside as the key components of PRHE. The findings indicate that PRHE effectively protects against the development of DN by retaining mitochondrial redox equilibrium via the regulation of PGC-1α-SIRT3-SOD2 signaling. This study creates an opportunity to develop this agricultural waste into a useful health product for diabetes.

Distant organ liver damage after acute kidney injury (AKI) remains a serious clinical setting with high mortality. This undesirable outcome may be due to some hidden factors that can intensify the consequences of AKI. Exposure to bisphenol A (BPA), a universal chemical used in plastics industry, is currently unavoidable and can be harmful to the liver. This study explored whether BPA exposure could be a causative factor that increase severity of remote liver injury after AKI and examined the preventive benefit by N-acetylcysteine (NAC) in this complex condition. Male Wistar rats were given vehicle, BPA, or BPA + NAC for 5 weeks then underwent 45 min renal ischemia followed by 24 h reperfusion (RIR), a group of vehicle-sham-control was also included. RIR not only induced AKI but produced liver injury, triggered systemic oxidative stress as well as inflammation, which increasing severity upon exposure to BPA. Given NAC to BPA-exposed rats diminished the added-on effects of BPA on liver functional impairment, oxidative stress, inflammation, and apoptosis caused by AKI. NAC also mitigated the abnormalities in mitochondrial functions, dynamics, mitophagy, and ultrastructure of the liver by improving the mitochondrial homeostasis regulatory signaling AMPK-PGC-1α-SIRT3. The study demonstrates that NAC is an effective adjunct for preserving mitochondrial homeostasis and reducing remote effects of AKI in environments where BPA exposure is vulnerable.

Sepsis-associated acute kidney injury (SA-AKI) presents a severe challenge in the elderly due to increasing incidence, high mortality, and the lack of specific effective treatments. Exploring novel and secure preventive and/or therapeutic approaches is critical and urgent. Berberine (BBR), an isoquinoline alkaloid with anti-inflammatory, antioxidant, and immunomodulatory properties, has shown beneficial effects in various kidney diseases. This study examined whether BBR could protect against SA-AKI in aged rats. Sepsis was induced in 26-month-old male Wistar rats by cecal ligation and puncture (CLP), either with or without BBR pretreatment. CLP induction led to SA-AKI, as indicated by elevated serum levels of malondialdehyde, tumor necrosis factor-alpha, urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL), along with histopathological features of kidney damage. Key indicators of kidney oxidative stress, mitochondrial dysfunction, apoptosis, and activations of the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling, including the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome pathway, were also elevated following CLP induction. BBR pretreatment substantially mitigated these adverse effects, suggesting that it protects against SA-AKI in aged rats by reducing oxidative stress, preserving mitochondrial integrity, and inhibiting key inflammatory pathways. These findings highlight the potential of BBR as a therapeutic agent for managing SA-AKI in elderly populations.

This study examined the potential benefits of melatonin against renal ischemia and reperfusion (IR) injury in obesity and explored the underlying mechanisms. Obesity was induced in Wistar rats by feeding a high-fat diet for 16 weeks. Three obese groups that underwent renal IR induction (30-min renal ischemia followed by 24-h reperfusion) were randomly assigned to receive melatonin at ischemic onset, reperfusion onset, or pretreatment for 4 weeks before IR induction. Groups of vehicle-treated obese and normal-diet-fed rats that underwent sham or IR induction were also included in the study. The results showed that renal functional and structural impairments after IR incidence were aggravated in obese rats compared to normal-diet-fed rats. The obese-IR rats also exhibited oxidative stress, mitochondrial dysfunction, apoptosis, and mitochondrial dynamics and mitophagy imbalances, which were all considerably improved upon melatonin treatment, irrespective of the treatment time. This study suggests the prophylactic and therapeutic efficacy of melatonin in IR-induced acute kidney injury (AKI) in obese individuals, which may improve the prognosis of AKI in these populations. The benefits of melatonin are likely mediated by the modification of various signaling molecules within the mitochondria that maintain mitochondrial redox balance and lead to the protection of mitochondrial homeostasis and integrity.

Human health hazards caused by bisphenol A (BPA), a precursor for epoxy resins and polycarbonate-based plastics, are well documented and are closely associated with mitochondrial impairment and oxidative imbalance. This study aimed to assess the therapeutic efficacy of N-acetylcysteine (NAC) on renal deterioration caused by long-term BPA exposure and examine the signaling transduction pathway involved. Male Wistar rats were given vehicle or BPA orally for 12 weeks then the BPA-treated group was subdivided to receive vehicle or NAC concurrently with BPA for a further 4 weeks, while the vehicle-treated normal control group continued to receive vehicle through to the end of experiment. Proteinuria, azotemia, glomerular filtration reduction and histopathological abnormalities caused by chronic BPA exposure were significantly reduced following NAC therapy. NAC also diminished nitric oxide and lipid peroxidation but enhanced renal glutathione levels, and counteracted BPA-induced mitochondrial swelling, increased mitochondrial reactive oxygen species production, and the loss of mitochondrial membrane potential. The benefit of NAC was related to the modulation of signaling proteins in the AMPK-SIRT3-SOD2 axis. The present study shows the potential of NAC to restore mitochondrial integrity and oxidative balance after long-term BPA exposure, and suggests that NAC therapy is an effective approach to tackle renal deterioration in this condition.