citrinin and Necrosis

Topics: Animals; Apoptosis; Cell Survival; Citrinin; Male; Mice; Necrosis; Sertoli Cells

The aim of this study was to establish the involvement of calcium signalling in genotoxicity, apoptosis and necrosis evoked by ochratoxin A (OTA) and citrinin (CTN) alone or in combination in porcine kidney PK15 cells. Cell proliferation test (MTT) and trypan blue assays (24 h) demonstrated that CTN (IC(50) = 73.5 ± 1.0, 75.4 ± 1.4 μM, respectively) was less toxic than OTA (IC(50) = 14.0 ± 2.4, 20.5 ± 1.0 μM, respectively). To test their cytotoxic interactions, two doses of single OTA (6 and 10 μM) and CTN (30 and 50 μM) and their combinations were applied. Combined treatment showed additive cytotoxic effects. OTA and CTN induced dose-dependent increase in cytosolic calcium level (assessed with Fura-2 AM). However, combined treatment did not provoke additional increase in calcium signal. The rate of apoptosis and necrosis (DAPI-antifade staining) was significantly higher after 12 h than 24 h, while the frequencies of micronuclei (MNs) and nuclear buds (NBs) were higher after 24 h than 12 h treatment. Combined exposure resulted in apoptotic and necrotic synergism, while genotoxic effects of OTA + CTN were noted as antagonistic or additive. Co-exposure of cells to calcium chelator BAPTA-AM significantly reduced CTN and OTA + CTN-evoked apoptosis. Twenty-four hour after co-exposure to BAPTA-AM and a single OTA and CTN, MNs significantly decreased while NBs dropped significantly after co-treatment with BAPTA-AM and OTA + CTN. In conclusion, disturbance of Ca(2+) homeostasis caused by OTA and CTN plays a significant role in cell genotoxicity and death.

Topics: Animals; Apoptosis; Calcium; Calcium Signaling; Cell Line; Cell Proliferation; Chromatin; Citrinin; Dose-Response Relationship, Drug; Drug Synergism; Epithelial Cells; Inhibitory Concentration 50; Kidney; Mutagenicity Tests; Necrosis; Ochratoxins; Swine; Time Factors

The toxic effects of citrinin in turkeys and ducklings was studied in four trials. Citrinin dissolved in dimethyl sulfoxide-70% ethanol solution (3:1, volume/volume) was administered by gavage to male turkey poults and male white Pekin ducklings. When seven-day-old ducklings were given doses of citrinin between 30 to 110 mg/kg body weight, most of the treated ducklings which died (49/80) did so within four to 12 hours. Blood samples were collected sequentially at 3, 6, 12, and 24 hours after administration from seven-day-old ducklings given the single lethal dose (LD50). The alterations included hyperkalemia (P less than or equal to 0.01) and metabolic acidosis characterized by reduced blood pH (P less than or equal to 0.01) and base excess (P less than or equal to 0.01). Fourteen-day-old turkeys and ducklings given 56 or 57 mg/kg, respectively, were killed at 1, 3, 6, 12, 24, 48, and 72 hours after treatment. The principal alteration in both species was nephrosis that was more severe in turkeys than in ducklings. Tubular necrosis was the dominant lesion at three to 72 hours in turkeys and at six to 24 hours in ducklings. Hepatic and lymphoid lesions occurred in both turkeys and ducklings treated with citrinin.

Topics: Animals; Benzopyrans; Citrinin; Ducks; Kidney Diseases; Liver Diseases; Lymphatic Diseases; Male; Mycotoxins; Necrosis; Poultry Diseases; Rats; Turkeys

Topics: Animals; Basement Membrane; Benzopyrans; Citrinin; Kidney; Kidney Diseases; Kidney Tubules, Distal; Kidney Tubules, Proximal; Male; Necrosis; Organoids; Rats; Time Factors

Topics: Administration, Oral; Animals; Benzopyrans; Citrinin; Cricetinae; Injections, Intraperitoneal; Kidney; Lethal Dose 50; Male; Mesocricetus; Necrosis

Topics: Animals; Benzopyrans; Body Weight; Cecum; Citrinin; Guinea Pigs; Kidney Tubules, Proximal; Lethal Dose 50; Mice; Mycotoxins; Necrosis; Rabbits; Rats; Swine