Plasma alanine

The initial enthusiasm for tacrine and velnacrine, which are the anticholinesterases most studied clinically, has been tempered by the fact that not all patients respond. Most show the peripheral parasympathomimetic effects of cholinesterase inhibition, e.g. dyspepsia and diarrhoea, as well as nausea and vomiting, and about half of the patients develop hepatotoxicity with elevated levels of plasma alanine transaminase. While some peripheral effects can be attenuated with antimuscarinics that do not enter the brain, these add further side-effects and the drop-out rate from such trials is high (<75%) in most long-term studies. Donepezil appears to show less hepatotoxicity but its long-term value remains to be determined. 

Oral dose of 1000, 2500, or 4000 mg/kg BW maintained at 22°C or minus 5°C for 10 h after dosing No deaths. Mild intoxication and elevated plasma alanine amino-transferase activity holding temperature did not affect toxicity 8... 

In a recent study, DR mice exhibited lower inflammatory damage induced by LPS. Balb/c mice were subjected to 40% DR and challenged with 25 pg of LPS. The DR mice had attenuated increases in the proinflammatory cytokines consistent with the lower liver damage characterized by lower plasma alanine aminotranferase (ALT), aspartate aminotransferase (AST) and histopathological analysis. The DR mice also had higher circulating corticosterone, a mediator of antiinflammatory action in DR,... 

Evans, G. O., and L. C. Whitehom. 1995. Effects of pyridoxal 5 -phosphate on plasma alanine aminotransferase determinations in toxicological studies. Toxicology Letters 80 34—37. 

The use of restraining procedures may affect biochemical values in small and, to a lesser extent, large laboratory animals. Increased plasma alanine and aspartate aminotransferase activities associated with restraint during collection have been... 

Plasma alanine (mM) 0.5 0.5 falling steadily to 0.4 Rising sharply to 0.7... 

In a 21-day study, mice were given drinking water containing annatto extract (56 or 351 mg/kg) or the compound norbixin (0.8, 7.6, 66, or 274 mg/kg), and rats were given drinking water containing annatto extract (0.8, 7.5 or 68 mg/kg) or norbixin (0.8,8.5, or 74 mg/kg). In rats, no toxicity was detected by plasma chemistry. In mice, norbixin induced an increase in plasma alanine aminotransferase activity (Fernandes et al. 2002). 

Centrilobular hepatic necrosis by single doses of coumarin (1,2-benzopyrone, ds-o-coumarinic acid lactone) have been reported in the rat (Lake 1984, Lake et al. 1989, Fentem et al. 1992), whereas chronic administration resulted in bile duct lesions (Hagan etal. 1967, Cohen 1979, Evans etal. 1989). The mechanism of acute coumarin-induced hepatotoxicity in the rat has been investigated by comparing the effects of coumarin with those of a number of methyl-substituted coumarin derivatives (Lake etal. 1994). Coumarin administration produced dose-related hepatic necrosis and a marked elevation of plasma alanine aminotransferase and aspartate aminotransferase activities. In contrast, non of the coumarin derivatives examined produced either hepatic necrosis or elevated plasma transaminase activities. Coumarin reduced hepatic microsomal ethylmorphine N-demethylase and 7-ethoxycoumarin 0-deethylase activities, whereas one or both mixed function oxidases appeared to be induced by treatment with 3,4-dimethylcoumarin, 4-methylcoumarin, 3-methyloctahydrocoumarin and 4-methyloctahydrocoumarin. These results provides an evidence that acute coumarin-induced hepatotoxicity in the rat is due to the formation of a coumarin 3,4-epoxide intermediate. 

When deprived of dietary choline, healthy male subjects have diminished plasma concentrations of choline and phosphatidylcholine, and they develop liver cell death (elevated plasma alanine aminotransferase). In similarly deprived animal models, the liver cell death is caused by apoptosis, a regulated form of cell suicide. In an ongoing study of choline deficiency in humans, muscle cell death (elevated plasma creatine phosphokinase, MM form) has also been noted. 

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