calpain and Rhabdomyolysis

The purpose of this study was to assess the role of caspase-dependent apoptosis, caspase 1, calpain 1, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) and the protective effect of grape seed proanthocyanidin extract (GSPE) in the development of rhabdomyolysis-induced acute kidney injury (AKI).. Twenty-one rats were divided into 3 groups - control, rhabdomyolysis and rhabdomyolysis + GSPE. Rhabdomyolysis was induced in the rhabdomyolysis and rhabdomyolysis + GSPE groups with the injection into both hind limbs of 10 ml/kg hypertonic (50%) glycerol following 24-hour dehydration on the 6th day. The rhabdomyolysis + GSPE group was given GSPE at 100 mg/kg by gavage for 7 days. The experiment was concluded 48 h after glycerol injection. Blood specimens were collected, and kidney tissues were extracted for histopathological examination.. We identified an increase in blood urea nitrogen, creatinine, histopathological score, iNOS, caspase 3, caspase 1 and calpain 1 expression in the rhabdomyolysis group compared to the controls and a decrease in eNOS expression. In the rhabdomyolysis + GSPE group, however, there was a decrease in these mediators, together with an increase in eNOS expression.. This study shows for the first time in the literature that calpain 1 is involved in the pathogenesis of rhabdomyolysis-induced AKI, and that GSPE may have a renoprotective effect.

Topics: Acute Kidney Injury; Animals; Apoptosis; Calpain; Caspase 1; Caspase 3; Disease Models, Animal; Female; Grape Seed Extract; Kidney; Necrosis; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Proanthocyanidins; Rats; Rats, Sprague-Dawley; Rhabdomyolysis; Time Factors

To clarify the involvement of calpains in sarcolemmal remodeling, we examined the expression of calpains and their substrate, alpha-fodrin, in various disorders of muscle. Although immunohistological reactions for alpha-fodrin and calpains were weak in normal control muscles, intense immunoreactivity for alpha-fodrin at the sarcolemma and for calpains throughout the cytoplasm were detected in small muscle fibers from patients with inflammatory myositis (IM), rhabdomyolysis (Rhab), and Duchenne muscular dystrophy (DMD). Most of the calpain-alpha-fodrin double-positive muscle fibers in IM and Rhab also expressed the developmental form of myosin heavy chain. The sarcolemma of these small muscle fibers reacted with an antibody that specifically recognizes the 150-kDa fragments of alpha-fodrin (SBDP 150s) cleaved by calpain, but not caspase 3. Western blot analysis confirmed these results. These observations indicate that calpain is activated and reacts with alpha-fodrin as a substrate at the sarcolemma, and plays a key role in modulating sarcolemmal proteins to adapt to the specific conditions in each myopathy.

Topics: Adult; Aged; Antibody Specificity; Calpain; Carrier Proteins; Child; Child, Preschool; Female; Humans; Immunohistochemistry; Male; Microfilament Proteins; Middle Aged; Muscle, Skeletal; Muscular Diseases; Muscular Dystrophy, Duchenne; Myosin Heavy Chains; Myositis; Peptide Fragments; Rhabdomyolysis; Sarcolemma

Topics: Adult; Animals; Blotting, Western; Calpain; Female; Humans; Immunohistochemistry; Isoenzymes; Male; Meat; Muscle Proteins; Muscle, Skeletal; Quail; Rhabdomyolysis

Myonephropathic metabolic syndrome (MNMS) is a serious muscle reperfusion injury associated with acute renal failure. The exact pathogenesis of MNMS has not been fully elucidated, nor effective treatment, through the renal failure is thought to be a consequence of rhabdomyolysis. In the present study, the possible involvement of calpain in the lysis was investigated in a MNMS animal model employing a cell permeable calpain antagonist calpeptin. Male rabbits were subjected to bilateral hind leg ischaemia for 5 hours by clamping the distal aorta, followed by reperfusion for 3 hours. Blood pressure, plasma N-acethyl-beta-D-glucosaminidase (NAG) and the presence of myoglobinuria were serially determined. Blood pressure remained constant during the ischemic period but dropped by about 25% immediately after reperfusion. This was significantly attenuated by intraaortic administration of calpeptin. NAG gradually increased during ischemia and during reperfusion and this was also significantly reduced by calpeptin. Myoglobinuria appeared immediately after reperfusion, and was also attenuated by calpeptin. Calpeptin prevented lytic and degenerative changes of the hind leg muscles, determined by light and electron microscopy. Thus it is concluded that activation of calpain in skeletal muscle is an important etiologic factor of MNMS and that the occurrence of MNMS may be prevented by administration of a calpain antagonist.

Topics: Acetylglucosaminidase; Acute Kidney Injury; Animals; Calpain; Dipeptides; Hindlimb; Male; Muscles; Rabbits; Reperfusion Injury; Rhabdomyolysis; Syndrome