In vivo effect of cinnarizine on acute hepatic damage in mice

This study aimed to investigate the effect of cinnarizine, a drug used for the treatment of motion sickness and which has direct anti-dopaminergic features [Dopamine Dl and D2 receptor blockade], on the acute hepatic injury in mice. Hepatotoxicity was induced by CCI4 orally [0.28 ml/100 g given twice with one week apart]. Cinnarizine at three dose levels [5, 10 or 20 mg/kg] or silymarin [22 mg/kg] were given orally daily for 14 days. starting at the time of administration of CCI4. Liver damage was assessed by determining liver serum enzyme activities and by hepatic histopathology. Cinnarizine decreased the increases in serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP] and also prevented the development of hepatic necrosis caused by CCI4. The effect of cinnarizine was a dose-dependent one. Cinnarizine administered at 10 or 20 mg/kg caused significant reduction in the elevated plasma ALT by 32.7, 34.3%, AST by 18.8, 34.7% and ALP by 32.8, 42.9%, respectively. In comparison, the elevated serum ALT, AST and ALP levels were decreased by 42.1%, 37.9% and 43.4% of controls, respectively by 22 mg/kg of silymarin. Histopathologic examination of the livers of CCI4-treated mice administered cinnarizine at 20 mg/kg showed marked restoration of the normal architecture of the liver tissue with minimal fibrosis. It is concluded that administration of cinnarizine in a model of liver injury induced by CCI4 results in less liver damage

gastric mucosal protective effects of pentoxifylline in the rat

The effects of pentoxifylline [PTX], a non-specific phosphodiesterase inhibitor were examined in rat models of gastric mucosal injury. Gastric mucosal damage was evoked in pylorus-ligated rats by subcutaneous [s.c.] administration of 20 mg/kg indomethacin together with oral administration of 2m 0.15 N HCI, by oral administration of acidified acetylsalicylic acid [200 mg/kg in 2 ml 0.15 N HCI] or by oral administration of l ml of 50% ethanol. The results showed that PTX [36 or 72 mg/kg, i. p.] given prior to indomethacin, acidified acetylsalicylic acid or 50% ethanol prevented the development of gastric mucosal damage by the ulcerogenic agents in a dose-dependent manner. In addition, PTX [36 or 72 mg/kg, i. p.] given to pylorus-ligated rats decreased gastric acid secretion. It is concluded that, PTX, when given at doses comparable to those used in man for treatment of circulatory disorders displayed anti-ulcerogenic activity in the rat in vivo

Evaluation of the gastric mucosal effects of different antidepressant drugs in the rat

Investigations were performed in the rat to evaluate the effects of different classes of antidepressant drugs on the gastric mucosal damage evoked by indomethacin and on gastric acid secretion. Following pylorus-ligation, indomethacin [20 mg/kg] was given subcutaneously and rats received 2 ml of 0.15 N HCI into their stomachs. Immediately afterwards, the drugs under study were given by the subctaneous route. Rats were killed 4 h after pylorus-ligation, and the number of gastric mucosal lesions were noted, their severity calculated and gastric acid secretory responses determined. The selective 5-hydroxytryptamine [serotonin] reuptake inhibitors [SSRIs] fluoxetine and sertraline caused dose-related increase in the degree of gastric mucosal injury caused by indomethacin. Similar effects were seen on administration of the heterocyclic agent; trazodone. In contrast, the indomethacin-induced lesion scores were remarkably reduced in rats treated with the non-selective noradrenaline and, serotonin reuptake inhibitors; imipramine and amitriptyline. Gastric acid secretion was increased by fluoxetine and sertraline administration, but reduced in rats treated with imipramine or amitriptyline. It is concluded that in the rat, the SSRIs fluoxetine and sertraline and the atypical antidepressant, trazodone, potentiate gastric mucosal damage caused by indomethacin in the presence of acid in the stomach. These results also suggest that changes in gastric acid secretion are involved in the modulatory effects induced by antidepressant drugs on gastric mucosal injury

protective effect of melatonin, Silymarin and their combination in experimental induced acute hepatotoxicity

The present study aimed to evaluate the hepatoprotective and curative effects of melatonin, silymarin and their combination on the carbon tetrachloride [CCI 4] induced hepatotoxicity. Different groups of rats received either melatonin [1 mg/kg], silymarin [22 mg/kg] or their combination once daily oral dose for successive ten days before exposure to CCI 4 then blood was obtained from all rats for biochemical tests 72 h later. In other groups, melatonin, silymarin and their combination were given also after treating the rat with CCI 4 to evaluate their effect on the course of established hepatic injury. Drugs were given once daily oral dose for ten days on the next day after CCI 4 treatment, in addition in further groups the effect of melatonin, silymarin or their combination on the normal rats [not treated with CCI 4] were examined, drug were given once daily oral dose for 10 days. When melatonin, silymarin and their combination were given before exposure to CCI 4 decrease in serum levels of ALT, AST, ALP was observed compared with Cd4 treated rats. Silymarin being most effective in this respect. In comparison, more marked reduction of serum enzyme level was observed in rats that received silymarin, melatonin and their combination after exposure to CCI 4, silymarin proved to be more effective than melatonin, while the combination did not provide additional benefit