Effect of metformin on clastogenic and biochemical changes induced by adriamycin in Swiss albino mice.
Diabetes mellitus (DM) is a chronic disease that is characterized by deteriorating glycemic control. The disease is known to be caused by imbalance between reactive oxygen species (ROS) and antioxidant defense systems. Hyperglycemia is commonly observed in a wide variety of diseases, including cancer. Although, therapy against glycemic control, is used in all these diseases, the diabetic cancer patients are on additional therapy with anticancer drugs. The objective of present study was to study if Glucophage (metformin), a very popular antidiabetic agent can avert the mutagenicity and lipid peroxidation caused by adriamycin (ADR), which is a commonly used cytotoxic drug. The experimental protocol included oral treatment of mice with different doses (62.5, 125 and 250 mg/kg day) of metformin for 7 days. Some mice in each group were injected i.p. with ADR (15 mg/kg). In each case animals were killed, 30 or 24, 48 and 72 h after the last treatment and femurs were excised for cytological studies by micronucleus test. Additional experiments on estimation of glutathione (GSH) and malondialdehyde (MDA) were undertaken in blood and serum, respectively. Twenty-four hour after the treatment, blood from each mouse was collected from heart and preserved for analysis. The results obtained revealed that pretreatment with metformin: (i) reduced the ADR-induced frequency of micronuclei without any alteration in its cytotoxicity and (ii) protected against the ADR-induced increase and decrease of MDA and GSH, respectively. The exact mechanism of action is not known, however, the inhibition of ADR-induced clastogenicity and lipid peroxidation by metformin may be attributed to the antioxidant action of the latter. Our results demonstrate that metformin might be useful to avert secondary tumor risk by decreasing the accumulation of free radicals and inhibition of mutagenicity.
Aleisa
A M
AM
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Al-Rejaie
S S
SS
Bakheet
S A
SA
Al-Bekari
A M
AM
Al-Shabanah
O A
OA
Al-Majed
Abdulhakeem
A
Al-Yahya
Abdulaziz A
AA
Qureshi
S
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D004317:Doxorubicin / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D015162:Micronucleus Tests
D000903:Antibiotics, Antineoplastic; D008315:Malondialdehyde; D004317:Doxorubicin; D008687:Metformin; D005978:Glutathione