Protective role of lipoic acid on methotrexate induced intestinal damage in rabbit model

Abstract

Methotrexate (MTX), a folate antagonist agent, is mainly used in treatment of malignant tumors and auto immune diseases and affects not only tumor cells, but also gastrointestinal mucosa. The present study was undertaken to determine whether lipoic acid (LA) could ameliorate methotrexate-induced oxidative intestine injury in rabbits. Twenty-one rabbits were randomly assigned into three groups: Group 1 (control group), Group 2 (received 20 mg/kg MTX), Group 3 (received MTX plus LA 75 mg/kg orally). On the 6th day rabbits were anesthetized and intestinal tissue sampled for pathologic and biochemical assessment. The intestinal tissue injury index and malondialdehyde (MDA) levels were lower in MTX+LA group as compared to the MTX group, and tissue glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were higher in MTX+LA group than in the MTX group (p < 0.05). These findings suggest that co-administration of LA with MTX is associated with reduction in oxidative injury and tissue damage in the intestine. We suggest that lipoic acid may have a protective role in the MTX-induced oxidative injury.

Histological Study on the Effect o fMethotrexate on the Oral Tissues of Aadult Male Rabbits

“…This is due to increase in the cell death and decrease in the cell number. (8,9) The loss of architecture, inflammatory infiltration, disarrangements of acini ,vacuolation in the acinar cells of the minor salivary glands in the buccal mucosa, floor of the mouth is in agreement of the other studies which show that methotrexate induces loss of architecture, with disarrangements and marked swelling of the acini. (4) These marked changes in the minor salivary glands of oral mucosa suggests suppression and or disruption of protein synthesis of abnormal protein this can lead to formation of cytolysosome, some may be an evidence of the distinctive process called shrinkage necrosis ,this process has been described as apoptosis in a number of tissues and the apoptotic bodies which are found in small numbers in normal tissues and greatly increased in tissues which have been subjected to chemotherapy.…”

“…Being a high affinity inhibitor of dihydrofolate reductase, methotrexate is a pro-oxidant compound that causes depletion of the dihydrofolate pool and directly affects the synthesis of thymidilate ,suppressing DNA synthesis .Therefore methotrexate affects not only tumor cells but also rapidly dividing cells such as gastrointestinal mucosa ,where it inhibits epithelial proliferation and induce apoptosis. (8,15,16) Recently, it has demonstrated that methotrexate causes significant reduction in the antioxidant enzymes levels, sensitizing the cells to reactive oxygen species (ROS). (17) The decrease in the weight of the animals in group II and Group III after treatment is mostly due to the loss of appetite due to the anti cancer therapy (Table 1).…”

“…The histological appearance of the floor of mouth shows distortion and loose attachments of the submucosa to the underlying muscle Figure (8).…”

The effect of quince leaf (<i>Cydonia oblonga</i> miller) decoction on testes in hypercholesterolemic rabbits: A pilot study

“…The rabbits in group 2 (hypercholesterolemia plus quince treatment) drank and tolerated the decoction (100 ml/each). At the end of the experimental study (12 th week), the animals were sacrificed with an anesthetic overdose of ketamine plus acepromazine (Somi et al, 2011). Thereafter, the left testis was immediately resected, then washed with 0.9% NaCl, cut into 5 × 5 mm pieces and fixed in 10% neutral buffered formaldehyde.…”