The effects of orchidectomy on toxicological responses to dietary ochratoxin A in Wistar rats

Mor, Firdevs; Kılıç, Mehmet; Yılmaz, Mesut; Eker, Ilknur; Uran, Kemal

doi:10.1016/j.etp.2014.04.002

Cited by 14 publications

(14 citation statements)

References 41 publications

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“…Karyomegaly is the most common and characteristic pathological finding in liver and kidney cells after OTA exposure [35]. However, there is no knowledge of pancreatic cell reactions after OTA treatment.…”

Section: Discussionmentioning

confidence: 99%

Diabetogenic Effects of Ochratoxin A in Female Rats

Mor

Sengul

Topsakal

et al. 2017

Toxins

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In this study, the diabetogenic effects of long term Ochratoxin A (OTA) administration in rats were investigated, and its role in the etiology of diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these purposes. The rats were divided into three different study and control groups according to the duration of the OTA administration. The rats received 45 μg OTA daily in their feed for 6, 9 and 24 weeks, respectively. Three control groups were also used for the same time periods. Blood and pancreatic tissue samples were collected during the necropsy at the end of the 6, 9 and 24 weeks. The plasma values of insulin, glucagon and glucose were determined for the study and control groups. Pancreatic lesions were evaluated via histopathological examination and insulin and glucagon expression in these lesions was subsequently determined using immunohistochemical methods. Statistically significant decreases in insulin levels were observed, in contrast to increases in blood glucagon and glucose levels. Histopathological examinations revealed slight to moderate degeneration in Langerhans islet cells in all OTA-treated groups. Immunohistochemistry of pancreatic tissue revealed decreased insulin and increased glucagon expression. This study demonstrated that OTA may cause pancreatic damage in the Langerhans islet and predispose rats to DM.

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Section: Discussionmentioning

confidence: 99%

Diabetogenic Effects of Ochratoxin A in Female Rats

Mor

Sengul

Topsakal

et al. 2017

Toxins

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“…Besides sex hormones, Pept1 and Pept2 expression was shown to be decreased due to thyroid regulation (tri-iodothyronine, T 3, and thyroxine, T 4 ) (Lu and Klaassen, 2006). On the other hand, some studies have demonstrated that OTA could interfere with hormone production (Frizzell et al, 2013, Gharbi et al, 1993, Hassan et al, 2010, Kumar et al, 2011, Mor et al, 2014, Woo et al, 2013. However, OTA-induced effect is uncertain because different models (in vitro or in vivo), doses or time of exposure have been used.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Sex differences in ochratoxin a toxicity in F344 rats after 7 and 21 days of daily oral administration

Pastor

Vettorazzi

Enciso

et al. 2018

Food and Chemical Toxicology

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Ochratoxin A (OTA) is a potent renal carcinogen in male rats but not in females. The mechanisms underlying these differences are unknown. The sex-dependent response of F344 rats after a repeated OTA oral administration for 7 (0.50 mg/kg bw) or 21 days (0.21 and 0.50 mg/kg bw) was evaluated. General toxicity, sex and thyroid hormones and histopathology were studied. OTA was quantified (HPLC-FLD) in plasma, kidney and liver and the expression of kidney transporters (RT-qPCR) was studied. After 7 days, kidney histopathology showed more pronounced signs of toxicity in males than in females. After 21 days, a higher toxicity was observed but sex differences disappeared. OTA concentration in plasma and tissues was similar in both sexes. Downregulation was the general OTA-induced effect. Oats' downregulation was slow in males and Oat3 did not change in females. Oatp1 was strongly downregulated in males after 21 days. An opposite effect was observed in Bcrp after 21 days: downregulation in males and upregulation in females. Females showed a dose- and time-dependent decrease of progesterone. Despite the sex differences, the final balance in OTA toxicokinetics at renal cell level does not seem to support a higher accumulation of OTA in male kidneys.

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“…OTA mainly damages the kidney and liver of animals, and the kidney is the first target organ. Mor et al found that in 16-week-old rats, after 6 weeks of OTA at 5 mg/kg, their body weight (BW) was slightly decreased compared with that of the control group [36]. Hope et al found that the urine output of the OTA-exposed group increased compared with that of the healthy control group [37].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway

et al. 2020

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The present study aimed to investigate the effects of astaxanthin (ASX) on ochratoxin A (OTA)-induced renal oxidative stress and its mechanism of action. Serum kidney markers, histomorphology, ultrastructural observation, and oxidative stress indicators were assessed. Meanwhile, quantitative real-time reverse transcription PCR and western blotting detection of NRF2 (encoding nuclear factor, erythroid 2 like) and members of the NRF2/KEAP1 signaling pathway (KEAP1 (encoding Kelch-like ECH-associated protein), NQO1 (encoding NAD(P)H quinone dehydrogenase), HO-1 (encoding heme oxygenase 1), γ-GCS (gamma-glutamylcysteine synthetase), and GSH-Px (glutathione peroxidase 1)) were performed. Compared with the control group, the OTA-treated group showed significantly increased levels of serum UA (uric acid) and BUN (blood urea nitrogen), tubular epithelial cells were swollen and degenerated, and the levels of antioxidant enzymes decreased significantly, and the expression of NRF2 (cytoplasm), NQO1, HO-1, γ-GCS, and GSH-Px decreased significantly. More importantly, after ASX pretreatment, compared with the OTA group, serum markers were decreased, epithelial cells appeared normal; the expression of antioxidant enzymes increased significantly, NQO1, HO-1, γ-GCS and GSH-Px levels increased significantly, and ASX promoted the transfer of NRF2 from the cytoplasm to the nucleus. These results highlight the protective ability of ASX in renal injury caused by OTA exposure, and provide theoretical support for ASX’s role in other mycotoxin-induced damage.

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The effects of orchidectomy on toxicological responses to dietary ochratoxin A in Wistar rats

Cited by 14 publications

References 41 publications

Diabetogenic Effects of Ochratoxin A in Female Rats

Diabetogenic Effects of Ochratoxin A in Female Rats

Sex differences in ochratoxin a toxicity in F344 rats after 7 and 21 days of daily oral administration

Protective Effect of Astaxanthin on Ochratoxin A-Induced Kidney Injury to Mice by Regulating Oxidative Stress-Related NRF2/KEAP1 Pathway

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