Effect of Metformin on Doxorubicin-Induced Memory Dysfunction

Ibrahim Alharbi,Yasser Almogbel,Ahmad Alhowail,Hindi Alharbi,Abdullah Alalwan

doi:10.3390/brainsci10030152

Abstract

Doxorubicin (DOX) is widely used to treat many types of cancer; however, it is associated with chemotherapy-related complications such as cognitive dysfunction, known as chemobrain. Chemobrain affects up to 75% of cancer survivors, and there are currently no available therapeutic options. This study aims to examine whether metformin (MET) can protect against the neurotoxicity caused by DOX treatment. Forty male rats were divided into four groups (10 rats/group): control, DOX, DOX + MET, and MET. Rats treated with DOX received five doses of 4 mg/kg DOX weekly (cumulative dose: 20 mg/kg). For the DOX-MET and MET groups, MET (3 mg/mL) was dissolved in drinking water. Behavioral and glucose tests were performed one day after treatment was completed. We found DOX (4 mg/kg/week, 5 weeks) caused learning and memory impairment in the Y-maze, novel object recognition, and elevated plus maze behavioral tests. MET did not rescue these DOX-induced memory impairments. Neither DOX nor MET nor MET + DOX altered glucose levels following the treatment. In summary, DOX treatment is associated with memory impairment in rats, but MET does not rescue this cognitive dysfunction.

Highlights

Recent advancements in chemotherapy have shown success in eradicating various types of cancer.The main mechanism underlying the action of chemotherapeutic agents is cytotoxicity
The toxicity associated with chemotherapy leads to several acute and chronic adverse side effects [1,2,3,4,5], including cognitive dysfunction, which is referred to as chemobrain [6]
Chronic DOX treatment did not affect the survival rate of rats; we found a higher incidence of death among the rats that received both DOX and MET (Figure 1A)

Summary

Introduction

Recent advancements in chemotherapy have shown success in eradicating various types of cancer.The main mechanism underlying the action of chemotherapeutic agents is cytotoxicity. Recent advancements in chemotherapy have shown success in eradicating various types of cancer. The toxicity associated with chemotherapy leads to several acute and chronic adverse side effects [1,2,3,4,5], including cognitive dysfunction, which is referred to as chemobrain [6]. The cognitive dysfunction can vary from moderate to severe and can affect patients’ emotional, behavioral, and mental status, which influences their ability to concentrate, multitask, and memorize [7]. There are over 16 million cancer survivors in the USA, and this number is expected to increase to 22 million by. As cognitive impairments affect up to 75% of cancer survivors [6], chemobrain remains a major clinical challenge.

Objectives

Results

Discussion

Conclusion