Alteration of the ATPase activity of skeletal muscle sarcolemma by in flamation and action of anti-inflammatory drugs

Skeletal muscle regeneration comprises several overlapping cellular processes, including inflammation and myogenesis. Prostaglandins (PGs) may regulate muscle regeneration, because they modulate inflammation and are involved in various stages of myogenesis in vitro. PG synthesis is catalyzed by different isoforms of cyclooxygenase (COX), which are inhibited by nonsteroidal anti-inflammatory drugs. Although experiments employing nonsteroidal anti-inflammatory drugs have implicated PGs in tissue repair, how PGs regulate muscle regeneration remains unclear, and the potentially distinct roles of different COX isoforms have not been investigated. To address these questions, a localized freeze injury was induced in the tibialis anterior muscles of mice chronically treated with either a COX-1- or COX-2-selective inhibitor (SC-560 and SC-236, respectively), starting before injury. The size of regenerating myofibers was analyzed at time points up to 5 wk after injury and found to be decreased by SC-236 and in COX-2−/− muscles, but unaffected by SC-560. In contrast, SC-236 had no effect on myofiber growth when administered starting 7 days after injury. The attenuation of myofiber growth by SC-236 treatment and in COX-2−/− muscles is associated with decreases in the number of myoblasts and intramuscular inflammatory cells at early times after injury. Together, these data suggest that COX-2-dependent PG synthesis is required during early stages of muscle regeneration and thus raise caution about the use of COX-2-selective inhibitors in patients with muscle injury or disease.

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Assessment of Gentamicin—Induced Nephrotoxicity in Rats Treated with Low Doses of Ibuprofen and Diclofenac Sodium

Clinical Science ◽

10.1042/cs0910187 ◽

1996 ◽

Vol 91 (2) ◽

pp. 187-191 ◽

Cited By ~ 9

Author(s):

M. M. Farag ◽

M. Mikhail ◽

R. Shehata ◽

E. Abdel-Meguid ◽

S. Abdel-Tawab

Keyword(s):

Serum Creatinine ◽

Atpase Activity ◽

Day Treatment ◽

Diclofenac Sodium ◽

Phospholipid Content ◽

Prolonged Administration ◽

Kidney Weight ◽

Urea Nitrogen ◽

Inflammatory Drugs ◽

Anti Inflammatory

1. The effects of two non-steroidal anti-inflammatory drugs, ibuprofen (20 mg day−1 kg−1) and diclofenac sodium (2.5 mg day−1 kg−1), on the severity of gentamicin-induced nephrotoxicity were evaluated in rats. 2. Administration of gentamicin (100 mg day−1 kg−1) for 5 days resulted in a significant increase in renal cortical total phospholipids accompanied by a significant decrease in cortical Na+, K+-ATPase activity. These changes were associated with a significant decrease in body weight and increases in kidney weight, serum creatinine and urea nitrogen. 3. In rats treated simultaneously with both gentamicin and either ibuprofen or diclofenac sodium for 5 days, all the measured parameters of renal dysfunction were similar in magnitude to those observed in rats treated with gentamicin alone. 4. In contrast, rats treated with either ibuprofen or diclofenac sodium for 27 days and injected concurrently with gentamicin during the last 5 days of the treatment period had significantly higher kidney weight, lower renal cortical Na+, K+-ATPase activity and higher cortical phospholipid content, serum creatinine and urea nitrogen than did rats treated with gentamicin alone. A 27-day treatment with ibuprofen or diclofenac sodium alone resulted in no change in renal function. 5. These results demonstrate that gentamicin nephrotoxicity was potentiated after the long (27 days) but not after the short (5 days) period of treatment with ibuprofen and diclofenac sodium. Thus, prolonged administration of non-steroidal anti-inflammatory drugs should be considered as a risk factor that may increase the nephrotoxic potential of gentamicin.

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