Potentiation of aflatoxin B1 induced hepatotoxicity in male Wistar rats with ethanol pretreatment

The interaction of ethanol and aflatoxin B1 (AFB1)-induced hepatotoxicity was studied in male Wistar rats using the activity of plasma GOT and GPT, liver triglyceride and histopathologic changes of liver necrosis as indices. Pretreatment of four oral doses of ethanol (4.0 g/kg BW each) at 48, 45, 24 and 21 hrs prior to AFB1 (0.5 to 2.0 mg/kg BW) single i.p. administration caused a significant increase in the activity of PGOT (6 folds) and PGPT (5 folds), liver triglycerides (2 folds) and severity of liver necrosis at 48 hrs after AFB1 administration. Ethanol pretreatment potentiated AFB1-induced hepatotoxicity by increasing MFO enzymes, aniline hydroxylase and p-nitroanisole-O-demethylase activity and lipid peroxidation, and decreasing in cytochrome b5, epoxide hydrolase activity and hepatic glutathione content. However, it did not cause any significant change in the activity of NADPH-cytochrome c reductase and glutathione-S-transferase and cytochrome P-450. These results suggest that potentiation of ethanol pretreatment on AFB1-induced hepatotoxicity may be due to an increase in the metabolic formation of AFB1-2, 3-oxide and subsequent binding to DNA.     

Time-course effects of ethanol pretreatment on hepatic necrosis and fat accumulation induced by aflatoxin B1 in the rat

Effect of ethanol pretreatment on acute hepatotoxicity and hepatic fat accumulation induced by aflatoxin B1 (AFB1) was followed up to 120 h in male Wistar rats. Pretreatment with 4 oral doses of ethanol (4.0 g/kg body wt. each) at 48, 45, 24 and 21 h prior to AFB1 (2.0 mg/kg body wt.) single intraperitoneal administration caused a significant increase in the activity of plasma glutamic oxaloacetic transaminase (PGOT, 2.4-fold), plasma glutamic pyruvic transaminase (PGPT, 2.8-fold), liver triglycerides (2.3-fold) and the severity of liver necrosis at 72 h after AFB1 administration. The effect of ethanol pretreatment on an increase in the accumulation of liver cholesterol and cholesterol esters induced by AFB1 is additive in nature. In a time-course study, it was shown that liver necrosis and triglyceride, cholesterol and cholesterol ester accumulation occurred simultaneously in both groups of rats treated with AFB1 and ethanol-AFB1. These results suggest that fat accumulation per se is not a primary cause of liver necrosis induced by AFB1 and ethanol-AFB1.     

Acute and subacute toxicity of cytochalasin E in the rat

Cytochalasin E, a minor toxic metabolite of the fungus Aspergillus clavatus, is acutely toxic to rats, mice, and guineapigs. The LD50 values for a single ip administration of cytochalasin E were: 1-day-old rats, 0.98 mg/kg; adolescent rats, 2.60 mg/kg; mice, 4.60 mg/kg, and guinea-pigs, 0.5–1.5 mg/kg. The toxicity of cytochalasin E was reduced in adolescent rats when administered orally (LD50 9.10 mg/kg) and was increased when administered by the intrathoracic route (LD50 1.30 mg/kg). Rats receiving a fatal ip dose of cytochalasin E died within 2–18 hr with 2–3 ml fluid in the peritoneal cavity. Intrathoracic administration of cytochalasin E killed rats within 2–8 hr and resulted in accumulation of 2.5–3.5 ml pleural fluid. Rats receiving the toxin orally died within 4–18 hr with 1.0–1.5 ml gastric fluid. Histopathologic examination revealed congestive degenerative changes, necrosis of liver, kidney, spleen, pancreas, and small intestine, brain edema, pulmonary hemorrhages, and injury to vascular walls.     

Reaction time, impulse speed, overall synaptic delay and number of synapses in tactile reaction neuronal circuits of normal subjects and thinner sniffers

In control subjects, warned auditory reaction time (RT) for a given effector organ was less than the warned visual RT for the same organ. The RT of the circuits between eye or ear or sites of tactile stimulation (SOS) and the index fingers were significantly shorter than that between eye or ear or the same SOS and the right or left big toes. The greater the distance between the SOS and the brain the longer the RT of the response by a given effector organ. The overall signal speed (OASS) from the neck to the index finger was less than that from the neck to the big toe. The OASS from the neck to a given effector was less than that from the toe to the same effector. Sensory nerve impulse speed was slightly faster than motor nerve impulse speed. The overall synaptic delay and estimated number of synapses (ENOS) of simple tactile reaction neuronal circuits of normal subjects did not significantly vary with site of tactile stimulation or effector organ. The mean number of synapses of various tactile reaction neuronal circuits of normal subjects was estimated to be between 69 and 77, which is far greater than the number of synapses in the touch-tactile and motor pathways combined. The overall synaptic delay in the tactile reaction neuronal circuits between SOS and the left and right big toes were significantly lower in sniffers than in control subjects. This may be due to a decrease in either the average synaptic delay, the number of synapses, or both in the tactile reaction neuronal circuits between sites of stimulation and big toes (but not index fingers) in sniffers.     

Antifertility effect of Citrus hystrix DC

An alcohol and chloroform extract of Citrus hystrix DC. fruit peel was investigated for antifertility activity in pregnant rats by oral administration at different periods of gestation. The extracts were found to effectively inhibit implantation, produce abortion and slightly hasten labor time when it was given from day 2 to 5, day 8 to 12 and day 15 until labor, respectively. At the same dose level which interrupted pregnancy, the extract did not affect the estrous cycle. Neither uterotrophic effects nor induction of vaginal cornification was observed when it was given to spayed rats. However, the extract enhanced the uterotrophic effect of estradiol when both were simultaneously given. Additionally, the extract stimulated uterine contractions observed in an in situ study. It is suggested that these two effects may be responsible for the interruption of pregnancy associated with the extract.     

Isolation and Purification of Cytochalasin E and Two Tremorgens from Aspergillus Clavatus

The nutritional quality of maize-soybean (70:30) tempe manufactured by culture fermentation by Rhizopus oligosporus and R. oryzae mixed in the ratio 1:1 was evaluated. Fermentation did not significantly change proximate composition. The dietary fibre increased on fermentation. Total iron, calcium and phosphorus concentrations did not change while the phytate content decreased by 67% and iron absorption increased 2.5 fold. Niacin, riboflavin and thiamine increased 2, 2.5 and 0.5-fold, respectively. The digestibility coefficient, protein efficiency ratio and net protein ratio improved to be comparable to skimmed milk. The overall acceptability of tempe gruel was similar to whole maize gruel. Maize-soybean tempe therefore has potential as a weaning food.     

Effect of ethanol on the in vivo covalent binding and in vitro metabolism of aflatoxin B1 in rats

The binding of [3H]aflatoxin B1 (AFB1) to the DNA, RNA and protein of liver after i.p. administration to rats with and without ethanol pretreatment was studied. The quantities of AFB1 binding to DNA and RNA were significantly increased by ethanol pretreatment but the formation of protein adducts was not affected. AFB1 metabolism by hepatic microsomes from ethanol-treated rats to aflatoxins M1 (AFM1) and Q1 (AFQ1) was increased when compared to those of control microsomes. These results suggest that an increase in AFB1 binding to liver nucleic acids and AFB1 metabolism after pretreatment of ethanol resulted from an increase in hepatic mixed-function oxidases and a possible decrease in hepatic glutathione (GSH) content which subsequently lead to an increase in hepatotoxicity of AFB1.     

The low calorie natural sweetener stevioside: Nephrotoxicity and its relationship to urinary enzyme excretion in the rat

The relationships between urinary enzyme levels and changes in blood urea nitrogen (BUN) and plasma creatinine levels, along with simultaneous ultrastructural changes of the kidney, were studied in rats treated with stevioside. BUN levels increased at 3 h onward after subcutaneous injection (s.c.) with stevioside (1.5 g/kg BW). The maximum increases in BUN and creatinine were approximately 180% and 132% at 9 h after stevioside injection, respectively. At this time, stevioside also caused significant increases in glucosuria, alkaline phosphatase (AP) and γ-glutamyl transpeptidase (γ-GTP) but no significant changes in proteinuria, N-acetyl-β-D-glucuronidase (NAG) or glutathione-S-transferase (GSH-S-TF). Histopathological examination of the kidney induced by stevioside revealed degeneration of the proximal convoluted tubule cells but no relation to lipid peroxide formation was detected. These results suggest that stevioside induced nephrotoxicity at the proximal convoluted tubules rather than at the glomeruli and other tubules presumably by a defect of cell volume regulation due to depletion of intracellular ATP and disruption of microvilli, and nuclear dysfunction.