Preclinical Efficacy of Melatonin to Reduce Methotrexate-Induced Oxidative Stress and Small Intestinal Damage in Rats

  title={Preclinical Efficacy of Melatonin to Reduce Methotrexate-Induced Oxidative Stress and Small Intestinal Damage in Rats},
  author={Viswa Kalyan Kolli and Premila Abraham and Bina Isaac and Narayanan Kasthuri},
  journal={Digestive Diseases and Sciences},
BackgroundMethotrexate is widely used as a chemotherapeutic agent for leukemia and other malignancies. The efficacy of this drug is often limited by mucositis and intestinal injury, which are the major causes of morbidity in children and adults.AimThe present study investigates whether melatonin, a powerful antioxidant, could have a protective effect.MethodRats were pretreated with melatonin (20 and 40 mg/kg body weight) daily 1 h before methotrexate (7 mg/kg body weight) administration for… 

Protective effect of melatonin against methotrexate-induced testicular damage in the rat model: An experimental study

Melatonin improves the epididymal sperm concentration by decreasing the expression of caspase-3 and increasing that of tyrosine-phosphorylated proteins in MTX-treated testes, indicating its protective effect against testicular damage induced by MTX.

Melatonin-lycopene combination improves methotrexate-induced liver toxicity in rats via anti-inflammatory effect

The LYC-MLT combination improved the acute toxic effects of MTX on the liver, and improved both liver function and the histopathology level, but oxidative stress parameters such as TOS and OSI did not change in MIT.

Protective effect of resveratrol against methotrexate-induced oxidative stress in the small intestinal tissues of rats.

Resveratrol and famotidine were found to significantly prevent elevation of the MDA, 8-OH/Gua and MPO parameters with MTX and decrease of the levels of tGSH in the duodenal and jejunal tissues.

Melatonin protects against cisplatin-induced ovarian damage in mice via the MT1 receptor and antioxidant activity†

Melatonin attenuated cisplatin-induced ovarian damage in mice, and the MT1 receptor could be used as a promising therapeutic target to the development of novel agents for preserving ovarian function during chemotherapy.

Influence of subacute melatonin treatment on antioxidant factors in the liver of female rats

Melatonin treatment causes changes in female rats liver functions and further investigations are necessary to examine the full impact of melatonin supplementation with regards to route of administration, dose as well as the exposure period.

Role of IL-6/STAT3 pathway in mediating the protective effect of agomelatine against methotrexate-induced lung/intestinal tissues damage in rats

By reducing oxidative stress, inflammatory processes, and modulating the IL-6/STAT3 pathway, Ago has potent ameliorative effects against MTX-induced lung/intestinal toxicities.

Nephroprotective Effect of Melatonin against Aluminum Phosphide Induced Renal Tissue Damage in Rats

It could suggest that the melatonin might be useful for preventing nephrotoxicity caused by aluminum phosphide through ameliorative effects on (especially parameters) biochemical indices, oxidative stress, histological and ultrastructural changes.

The effects of lycopene on intestinal injury due to methotrexate in rats

It is indicated that Lyc might be useful for protecting intestinal damage induced by Mtx in rats by reducing the increased oxidative stress and pro-inflammatory cytokine (IL-1β) levels.

Renoprotective Influence of Pomegranate Juice on Nephrotoxicity Induced by Methotrexate

  • A. H. Saaty
  • Medicine, Biology
    Journal of Pharmaceutical Research International
  • 2021
POJ exerted a potent nephroprotective action and prevent Metho-induced nephrotoxicity, and may has a beneficial effect in patients receiving Metho therapy.



Oxidative stress contributes to methotrexate-induced small intestinal toxicity in rats

It is suggested that oxidative stress plays an important role in the MTX-induced small intestinal damage, especially neutrophil infiltration, and the modulation of oxidative stress would be useful in reducing intestinal damage in MTX treatment.

Melatonin prevents methotrexate‐induced hepatorenal oxidative injury in rats

The present study suggests that melatonin may be of therapeutic benefit when used with MTX and elucidates the role of free radicals in MTX‐induced toxicity and the protection by melatonin.

L-Carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death

The results suggest that L-Car, possibly via its free radical scavenging and antioxidant properties, ameliorates MTX-induced oxidative organ injury and inhibits leukocyte apoptosis and may be promising in alleviating the systemic side-effects of chemotherapeutics.

Effects of N-acetylcysteine on methotrexate-induced small intestinal damage in rats.

Administration of N-acetylcysteine provides protection against the MTX-induced damage to small intestinal epithelium in rats, and this protective effect of NAC may have clinical applications in chemotherapy.

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

  • M. SomiB. Hajipour A. Vatankhah
  • Medicine, Biology
    Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology
  • 2011
It is suggested that lipoic acid may have a protective role in the MTX-induced oxidative injury, and co-administration of LA with MTX is associated with reduction in oxidative injury and tissue damage in the intestine.

Oxidative stress and enhanced paracellular permeability in the small intestine of methotrexate-treated rats

NAC protected the small intestine of rats from MTX-induced change in paracellular permeability, suggesting that ROS played an important role in the enhanced parace cellular permeability.

Protective effect of melatonin on indomethacin‐induced gastric injury in rats

The results suggest that the protection afforded by the pineal hormone against indomethacin‐induced gastric injury may be, in addition to other possible mechanisms, to its radical scavenging activity.

Melatonin ameliorates ionizing radiation-induced oxidative organ damage in rats.

Melatonin attenuates diabetes‐induced oxidative stress in rabbits

Melatonin attenuated diabetes‐induced alterations in glutathione redox state and HFR levels, normalized creatinine concentration and diminished urea content in serum and the examined organs, and the indole‐induced increase in the activities of the enzymes of glutathion metabolism might be of importance for antioxidative action of melatonin under diabetic conditions.