Diabetogenic Effects of Ochratoxin A in Female Rats

Abstract

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.

May phytophenolics alleviate aflatoxins-induced health challenges? A holistic insight on current landscape and future prospects

“…Additionally, there was no significant association between AFB1-adducts and the progression of other metabolic diseases such as central obesity, obesity, non-alcoholic fatty liver diseases ( 229 ). This result, however, was aligning with previous animal-based studies that confirmed the association between exposure to mycotoxins and the onset/progression of DM ( 219 ). The evidence imparts that fungal toxins may increase the susceptibility to the onset of MetSys; therefore, well-designed human-based studies are needed to show how mycotoxins and AFs may contribute to the progression of MetSys ( 213 , 230 ).…”

“…In an interesting study ( 219 ), it has shown that the long-term exposure to mycotoxins was significantly associated with DM development in affected rats ( 219 ). In this finding, OTA could remarkably increase blood glucose levels, cause damage to pancreatic islets, and decrease insulin secretion ( 219 ). The cross-talks between the progression of MetSys and prevalence of HCC have been widely investigated ( 220 , 221 ).…”

Risk assessment of ochratoxin A in food

“…The CONTAM Panel noted the inadequate study design and unclear reporting of the new studies (published after 2006) investigating the carcinogenic effects of OTA and considered that these provided only limited additional information on OTA carcinogenicity that could serve as a basis for quantitative risk assessment (Table 6 ). Long‐term OTA administration of OTA to female Wistar rats was reported to cause toxic effects on the endocrine pancreas, suggesting diabetogenic potential of OTA (Mor et al., 2017 ). These effects were evident at a dose higher than those required for nephrotoxicity and renal tumour formation (Table 6 ), and therefore did not provide a more sensitive endpoint of toxicity.…”

Membrane Receptor‐Mediated Disruption of Cellular Homeostasis: Changes in Intracellular Signaling Pathways Increase the Toxicity of Ochratoxin A

“…[ 13 ] A similar routine with OTA administration in rats was found to decrease blood insulin levels, increase glucose and glucagon levels, and induce moderate degeneration in pancreatic Langerhans islet cells. [ 14 ] After a pathological analysis, bile duct hyperplasia was observed in the microscopic examination after 26‐weeks of OTA treatment in male F344 rats, but not in rats exposed to OTA for 13‐weeks or less. [ 15 ] Longer‐term studies involving a larger number of experimental animals (up to 2 years) are reported in the National Toxicology Program and IARC documents.…”