Progression Of Nephrotoxicity Research Articles

The beneficial effects of Berberine on experimental model of Acrylamide induced nephrotoxicity

Background Acrylamide (AA) is an industrial monomer which is used in many industries. Dietary or occupational exposure affects high percentage of population. It causes multi-organ toxicity including neurotoxicity, hepatotoxicity and nephrotoxicity via induction of oxidative stress and inflammation. AA induced nephrotoxicity is a major health problem that needs our concern. Berberine (BBR) is an alkaloid that has nephroprotective effects as being an antioxidant and an anti-inflammatory. Aim The aim of this work was to shed light on autophagy and nucleotide binding oligomerization domain like receptor family pyrin domain containing 3 (NLRP3) inflammasome formation and to assess the ameliorating effect of BBR as antioxidant, anti-inflammatory and autophagy modulator on experimental model of AA induced nephrotoxicity. Materials and methods This study was done on 50 male rats, which were randomly divided equally into 5 groups: control group; Acrylamide group (received AA only); Berberine-Acrylamide co-treatment group (received AA and BBR simultaneously); prophylaxis group (given BBR alone for 10 days followed by BBR and AA for another 10 days); and Berberine group (received BBR only). Results Administration of BBR as a prophylactic agent enhanced kidney function, restored electrolyte balance, suppressed oxidative stress and NLRP3 inflammasome and induced mitophagy. However, its administration as a co-treatment with AA showed ameliorating effect. The histopathological changes were consistent with the biochemical results. Conclusion: BBR could protect against AA induced nephrotoxicity through reduction of oxidative stress, suppression of NLRP3 inflammasome and induction of mitophagy. The usage of BBR as a protective drug against the progression of nephrotoxicity seems to be promising.

Liposomal Artificial Red Blood Cell-Based Carbon Monoxide Donor Is a Potent Renoprotectant against Cisplatin-Induced Acute Kidney Injury.

Cisplatin (CDDP) is an essential anti-tumor agent for chemotherapeutic regimens against various types of cancer. However, the progression of nephrotoxicity, which is the main adverse effect of CDDP, leads to discontinuation of CDDP chemotherapy. Therefore, development of a renoprotectant against CDDP-induced nephrotoxicity is crucial. Here, the potential of a carbon monoxide (CO)-loaded hemoglobin-vesicle (CO-HbV) as a renoprotectant for CDDP-induced nephrotoxicity was evaluated for its renoprotective effects against CDDP-induced nephrotoxicity, inhibitory effects on the anti-tumor activity of CDDP, and anti-tumor activity. In healthy mice, after pretreatment with either saline, HbV, or CO-HbV prior to CDDP administration, only the CO-HbV pretreatment group ameliorated the progression of CDDP-induced nephrotoxicity by suppressing apoptosis via caspase-3. In experiments using B16-F10 melanoma cells, the half-maximal inhibitory concentration of CDDP decreased with co-incubation with CO-HbV, owing to the anti-tumor activity of CO. CO-HbV pretreatment had no impact on the anti-tumor activity of CDDP in B16-F10 melanoma cell-bearing mice, which was consistent with the results of the cell experiment. Furthermore, CO-HbV pretreatment improved body growth and survival rates. In conclusion, CO-HbV pretreatment is a potent renoprotectant for CDDP-induced nephrotoxicity, allowing treatment with CDDP to be conducted without failure of cancer treatment.

Clinicopathological and Tissue Indicators of Para-Aminophenol Nephrotoxicity in Sprague–Dawley Rats

A model of para-aminophenol (PAP) nephrotoxicity in Sprague-Dawley rats was utilized to characterize potential indicators of toxicity in the kidney and in biofluids, and to chronicle the progression of acute renal injury. Rats were administered PAP at a low or high dose and examined terminally at 6, 24 and 48 hours (4 animals/group with matching controls). Acute tubular necrosis was observed in the medullary rays (low and high doses) and the outer stripe of outer medulla (high dose only) as early as 6 hours postdosing. Starting at 24 hours, regeneration of the tubular epithelium was evident in both low and high dose studies. Associated with the tubular lesions, we observed elevation of urinary alpha -glutathione S-transferase levels, an indicator of proximal tubular injury. By immunohistochemistry of the kidney, decreased gamma -glutamylcysteine synthetase expression correlated with tubular injury, especially at high dose, whereas elevation of vimentin, osteopontin, and Ki-67 expression was concurrent with tubular regeneration. Clusterin and kidney injury molecule-1 displayed expression patterns characteristic of both renal injury and regeneration. Taken together, this study provided insight into the progression of nephrotoxicity, and allowed the evaluation of potential urinary and tissue protein biomarkers that could complement the early detection of acute tubular injury.

Major role of organic anion transporter 3 in the transport of indoxyl sulfate in the kidney

Indoxyl sulfate is a uremic toxin that accumulates in the body because of the patient's inability to excrete it and it induces a number of uremic symptoms and leads to chronic renal failure. The functional failure of the excretion system for indoxyl sulfate causes its accumulation in blood. The purpose of the present study was to characterize the transport mechanism responsible for the renal excretion of indoxyl sulfate. The [3H]indoxyl sulfate transport mechanism was investigated using an in vivo tissue-sampling single-injection technique, the kidney uptake index (KUI) method. Rat organic anion transporter 3 (rOAT3)-expressing Xenopus laevis oocyte system was used for measuring [3H]indoxyl sulfate uptake activity. Probenecid showed a concentration-dependent inhibitory effect on the uptake of [3H]indoxyl sulfate using the KUI method, and uptake was inhibited by organic anions such as para-aminohippuric acid (PAH) and benzylpenicillin, by weak base such as cimetidine, and by uremic toxins, such as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) and hippuric acid (HA). However, salicylic acid, indomethacin, 3,5,3'-triiodo-l-thyronine and indole acetic acid (IA) had no effect on the uptake. rOAT3-expressing oocytes exhibited uptake of [3H]indoxyl sulfate by rOAT3 (Km = 158 micromol/L). Moreover, a number of uremic toxins inhibited the uptake of [3H]indoxyl sulfate by rOAT3. These results suggest that rOAT3 is responsible for the renal uptake of indoxyl sulfate, and uremic toxins share the transport mechanism for indoxyl sulfate. Mutual inhibition of these uremic toxins via OAT3 may accelerate their accumulation in the body and, thereby, the progression of nephrotoxicity in uremia.