Histological evaluation of the role of atypical antipsychotic drugs in inducing non-alcoholic fatty liver disease in adult male albino rats (light and electron microscopic study).

Many of atypical antipsychotic drugs are associated with adverse metabolic effects, including fatty infiltration of the liver. This study aimed at studying the histological evaluation of the role of atypical antipsychotic drugs (olanzapine and aripiprazole) in adult male albino rats. Sixty adult male albino rats were divided equally into three groups. Group I served as a control while groups II and III were treated with olanzapine and aripiprazole consecutively. Sections of the liver were examined by light and electron microscopy. A highly significant increase in the weight of rats in olanzapine- and aripiprazole- treated groups in comparison to the control group was noticed. On the other hand, there was a highly significant increase in body weight of the olanzapine group in comparison to aripiprazole. Olanzapine- and aripiprazole-treated rats showed highly significantly increased fatty infiltration of liver (steatosis) compared with the control group. However, the aripiprazole-treated group showed less steatosis compared with olanzapine. The mean non-alcoholic steatohepatitis scoring and fibrosis of the olanzapine group were highly significantly increased compared to the aripiprazole group. Ultrastructurally, liver from the olanzapine group showed large fat droplets in perinuclear region, between cisternae of the rough endoplasmic reticulum, and in the space of Disse. Large-sized mitochondria and myelin figures were seen. Although histopathological changes of the liver in the form of non-alcoholic fatty liver disease were more prominent in the olanzapine group, they were also evident in the aripiprazole group.

Long-term homocysteine exposure induces alterations in spatial learning, hippocampal signalling and synaptic plasticity.

Abnormally high levels of homocysteine (HCY) have been linked to neurodegenerative diseases, but it remains unclear whether this is the cause or effect of degenerative processes. Here, we investigated the effects of prolonged HCY exposure on cognitive abilities and physiological parameters by injecting rats daily with either 20 or 200 mg/kg HCY over a period of up to 14 weeks. Notwithstanding a significant weight reduction in the 200 mg HCY group, HCY-exposed animals did not show a behavioural deficit when tested repeatedly (in weeks 1, 3, 5, 7 and 13) in a reference memory version of the water maze. Unexpectedly, some improvement in repeated reversal learning was observed in HCY exposed animals compared to controls. Pre-treatment with HCY for 3 weeks before water maze training did not uncover any cognitive alterations. Increased plasma concentrations of HCY were revealed only for the 200 mg HCY group after 14 weeks of injections, but no evidence for DNA damage was obtained. Immunocytochemically, HCY was detected in the brain after 14 weeks of treatment (both 20 and 200 mg/kg), but not after 5 weeks. Bidirectional changes in basic synaptic transmission and long-term potentiation of hippocampal CA1 pyramidal cells were observed at 5, 7 and 14 weeks in both HCY groups, indicative of complex, multifactorial time- and concentration-dependent changes. Overall, it is concluded that healthy adult rats are able to cope with continuous exposure to HCY. While HCY affects growth and neuronal excitability, this does not precipitate into an immediate impairment of cognitive function.