Abstract
Although cyclophosphamide (CP), an alkylating agent, has been extensively used in
chemotherapy, it possesses a wide spectrum of adverse effects including hepatotoxicity.
This study was aimed to evaluate the protective effects of Zataria multiflora against
hepatic damage induced by CP in mice.
Mice were orally (gavages) pretreated with the ethanolic extract aerial parts of Zataria
at doses of 50, 100, 200, or 400 mg/kg for 7 consecutive days before a single intraperitoneal
injection of 200 mg/kg CP. After 24 h, animals were anesthetized, blood samples and
hepatic tissues were collected and used for biochemical and histological examination.
Serum levels of hepatic markers were significantly increased after only CP treated
animals but restored in Zataria pretreated groups. A single dose of CP administration
also markedly induced abnormality in the levels of several biomarkers associated with
oxidative stress in liver tissues homogenates. However, pretreatment with Zataria
significantly inhibited the abnormality of antioxidant enzymes defense system in the
liver tissues. In addition, histopathological studies proved that CP causes damage
to the liver, and this was evidenced by the induced dilated and congested sinusoidal
space, lymphocytic infiltration between hepatocytes, portal space with moderate to
severe inflammation and necrotic hepatocyte with absence of nuclei. Zataria effectively
protected animals against CP-induced hepatic tissue damages.
Our results reveal that Zataria produces a potent hepatoprotective role and could
be a potent candidate to use concomitantly as a supplement agent against hepatotoxicity
of CP for the patients undergoing chemotherapy.
Key words
hepatoprotective - zataria multiflora - cyclophosphamide - liver toxicity - antioxidant
activity