Abstract
Background:
One of the primary concerns of the pharmaceutical industry is the potential for liver damage caused by drugs. Diclofenac is a member of the family ofnonsteroidall antiinflammatory medications (NSAIDs), which are known for their anti-inflammatory, antipyretic, and analgesic effects. Although it is commonly prescribed, liver damage is one of the primary risks associated with this medication. Therefore, it is necessary to use a prospective therapeutic medication that can counteract the cytotoxic impact of diclofenac. Humans have utilized natural items as a means of obtaining sustenance, maintaining their health, and treating a wide variety of illnesses. Antioxidant, anti-inflammatory, and liver-protective properties are associated with silymarin, which is a flavonoid chemical derived from the seeds of the Silybum marianum plant.

Aim:
This study aimed to evaluate the possible hepatoprotective effect of silymarin against diclofenac-induced liver injury.

Methods:
Forty Wistar rats were used in the current investigation and grouped randomly into four equal groups. The first group (G1) was kept as a control group. G2 received intraperitoneal injections of diclofenac (50 mg/kg. BW/day) for 5 days. G3 received oral silymarin for 5 days (200 mg/kg BW/day) dissolved in distal water. G4 received diclofenac plus silymarin with the same previously mentioned doses for 5 days. The animals were collected and subjected to histopathological examination.

Results:
The diclofenac-treated group showed several pathological changes within the hepatic parenchyma, including diffuse coagulative and hydropic degenerations with general disorganization of the hepatic cords, severe dilatation and congestion of the central vein and portal blood vessels, severe sinusoidal dilatation and congestions accompanied with severe pressure atrophy of the hepatic cords, and severe inflammatory cell infiltrations. Meanwhile, the diclofenac plus silymarin-treated group showed a significant good effect, where silymarin ameliorated almost all histopathological lesions induced after diclofenac treatment as mitigating the degenerative changes of hepatocytes, minimizing inflammatory cell infiltrations, and normal organized hepatic rays with normal sinusoids in between were distinguished.

Conclusion:
Silymarin has a significant hepatoprotective effect against diclofenac-induced hepatotoxicity through neutralization of all histopathological injuries.

Key words: Silymarin, Diclofenac, Hepatotoxicity, Hepatoprotective, Histopathological