Photomicrograph were taken from camera (Nickon, Japan) mounted microscope.12,13 Histological examination showed that there was swelling of hepatocytes, focal necrosis, zonal necrosis and ballooning degenerations.
Another interesting observation was regarding the pattern of severity of zonal necrosis on day 15th as compared to 30th day.
The histological findings of acute hepatitis and focal necrosis and zonal necrosis were reversed 10% to 20% in groups A2 and B2 at 30th days.
The US DILIN recognizes 18 distinct histologic damage categories: acute hepatitic, chronic hepatitic, acute cholestatic (Figure 3), chronic cholestatic (Figure 4, A and B), cholestatic-hepatitic, granulomatous, macrovesicular steatotic, microvesicular steatotic, steatohepatitic (Figure 5), zonal necrosis (Figure 1), nonzonal necrosis, vascular injury (Figure 6, A and B), hepatocellular alteration, nodular regenerative hyperplasia (Figure 7), mixed or unclassified injury, minimal nonspecific changes, absolutely normal, and massive necrosis.
An injury pattern that shows zonal necrosis suggests the involvement of zonally distributed enzymes in the pathogenesis.
Older case reports of lisinopril induced toxicity have shown similar histopathological findings of portal inflammation by lymphocytes without centrilobular zonal necrosis
. (9) There are various theories regarding possible mechanisms for DILI with lisinopril, namely terminal proline ring mediated bile stasis (8, 10) and hypersensitivity to the sulfhydryl group.
A stu-dy reported similar findings with co-administration NaF 4 mg/rat/day and 3 mg/rat/day vitamin E for 5 weeks.24 Nair showed that the administration of sod-ium fluoride and arsenic trioxide to rats for 30 days caused severe zonal necrosis
. In the same study during the withdrawal period administration of vitamin E showed amelioration in necrosis of hepatocytes 27.