Muscle Atrophy and Histopathology of the Soleus in 6-Mercaptopurine-Treated Rats

Abstract

6-Mercaptopurine (6-MP) is an immunosuppressive drug that is used in chemotherapy of acute leukemia. It is a known purine antagonist which interferes with the binding of adenine and hypoxanthine and thereby disturbs the synthesis of DNA and RNA (Elion, 1967;Malmud et al., 1972). Recently, neonatal treatment of Sprague-Dawley rats with 6-MP (2 mg/kg s/c 2-22 days postnatal) has been shown to cause severe atrophy of hind limb muscle in adult animals (Alleva, 1981). However, it is not known whether the atrophy is specific to certain muscle fiber types, nor is it clear whether the atrophy is induced by neurogenic or myogenic factors. The objective of this study was to observe the effect of neonatal 6-MP treatment on the sciatic nerve conduction to the soleus (SOL) and the fiber areas plus percent composition of the type-I (slow-twitch) and type II (fast-twitch) muscle fibers in the SOL of adult male and female rats. METHODSSix male and six female Sprague-Dawley rats were selected from larger groups that were treated neonatally between 2-22 days after birth with 6-MP-NaOH (2 mg/kg BW, daily, s/c). Another twelve litter-mates, 6 from each sex group, were injected with 0.9% saline during the same period to serve as controls (Alleva et al., 1981). The animals were housed under optimal laboratory conditions on ad libitum rat chow and water. After six months of age, the animals were anesthetized (chloral hydrate: 400 mg/kg BW i/ p) and the sciatic nerve conduction to the soleus was evaluated by employing monopolar electrodes according to the method of Herbison et al. (1973). The latency of conduction, the amplitude, duration -and phasicity of the action potential were noted in both the normal and 6-MP treated male and female rats. After

Musculoskeletal System

“…336 Examination of the soleus muscle in rats treated with 6-mercaptopurine showed fiber atrophy and variable degrees of fiber splitting in both type I and II fibers with increase in endomysial connective and fatty tissue. This is an immunosuppressive drug and purine antagonist, which interferes with the binding of adenine and hypoxanthine and disrupts the synthesis of DNA and RNA.…”