Nephrotoxicity evaluation and proteomic analysis in kidneys of rats exposed to thioacetamide

Abstract

Thioacetamide (TAA) was administered orally at 0, 10, and 30 mg/kg body weight (BW) daily to Sprague–Dawley rats aged 6–7 weeks for 28 consecutive days. Nephrotoxicity and proteomics were evaluated in the kidneys of rats exposed to TAA. The BW decreased, however, the relative kidneys weight increased. No significant histopathologic abnormalities were found in the kidneys. The numbers of monocytes and platelets were significantly increased. However, the mean corpuscular volume and hematocrit values were decreased significantly in rats exposed to 30 mg/kg BW TAA. The expression levels of Kim-1 and NGAL were increased 4 to 5-fold in the kidneys, resulting in significant nephrotoxicity. Proteomic analysis was conducted and a total of 5221 proteins spots were resolved. Of these, 3 and 21 protein spots were up- and downregulated, respectively. The validation of seven proteins was performed by Western blot analysis. The expression level of ASAP2 was significantly upregulated, whereas RGS14, MAP7Dl, IL-3Rα, Tmod1, NQO2, and MUP were reduced. Sixteen isoforms of MUP were found by the 2DE immunoblot assay and were significantly downregulated with increasing exposure to TAA. MUP isoforms were compared in the liver, kidneys, and urine of untreated rats and a total of 43 isoforms were found.

Gastrodia elata rhizoma ameliorates thioacetamide-induced liver injury in dogs

“…Besides its toxic effects on the liver, TAA is known to cause blood abnormalities, lipoprotein abnormalities [ 37 ], and kidney disorders [ 38 ]. Contrary to the present study, studies have reported that TAA causes a decline in the levels of RBCs and HB and an increase in WBC levels due to acute inflammation in response to chemicals such as TAA [ 39 , 40 ].…”

The ameliorating role of sofosbuvir and daclatasvir on thioacetamide-induced kidney injury in adult albino rats

“…Furthermore, fusion of cell margins, vascular degeneration and pyknotic nuclei were observed in the renal glomeruli and tubules after treatment with 0.3% of TAA in drinking water for two weeks [ 1 ]. However, no significant histopathologic abnormalities were detected in the kidneys of rats exposed to oral TAA at doses like 10 mg and 30 mg/kg body weight for four weeks or intraperitoneal injection with 25 mg/kg or 100 mg/kg body weight for 8 or 24 hours [ 9 , 41 ]. In previous research, TAA increased collagen deposition and induced glomerular sclerosis and necrosis with interstitial fibrosis [ 2 , 42 , 43 ].…”

“…Moreover, all the measured oxidative stress markers (MDA, SOD and GSH) and proinflammatory cytokines like TNF-α were markedly affected by TAA treatment. Several studies reported the disturbance in the renal function parameters, oxidative stress markers, cytokines and inflammatory markers as interleukins in the TAA-treated group [ 1 , 2 , 9 - 12 , 41 ]. Mostly, oxidative stress plays the most important role in TAA-induced nephrotoxicity so that many authors hypothesized that the use of antioxidants could have beneficial effects [ 47 , 48 ].…”