The non-steroidal anti-inflammatory drugs protect mouse cochlea against acoustic injury

Acoustic injury is a common cause of hearing loss for people in industrial societies. Cyclooxygenase (COX) and lipoxygenase (LOX) are two important enzymes involved in arachidonic acid metabolism. Two COX isozymes are characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression. Although COX-1, COX-2, and LOX are expressed in cochlea, their roles played in cochlear acoustic injury have not fully been evaluated. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit either COX or LOX, or both. This study evaluated the effects of NSAIDs on the functional recovery of the cochlea after acoustic injury. Mice were exposed to a 4-kHz pure tone of 128 dB SPL (sound pressure level) for 4 hours and received one of the following drugs for two weeks after acoustic overexposure: indomethacin (COX-1 inhibitor), meloxicam, SC58125, and CAY10404 (COX-2 inhibitors), and nordihydroguaiaretic acid (LOX inhibitor). The hearing ability was evaluated using an auditory brainstem response (ABR) before and after overexposure. The ABR threshold shifts, defined as subtraction between ABR thresholds before and after overexposure, were compared among the control and the medication groups at one and two weeks after acoustic overexposure. Treatment of mice with either indomethacin or nordihydroguaiaretic acid decreased the ABR threshold shifts after overexposure, indicating that COX-1 and LOX inhibitors exhibited protective effects against acoustic injury. In contrast, COX-2 inhibitors, meloxicam, SC58125, and CAY10404, showed no noticeable effects on the ABR threshold shifts. These findings suggest that COX-1 and LOX are involved in the pathogenesis of acoustic injury in cochlea.     

Nonsteroidal anti-inflammatory drugs

NSAID-associated dyspeptic symptoms are common and can be managed empirically with an H2-receptor antagonist or a proton-pump inhibitor. Treatment of established gastroduodenal ulcers is accomplished best by withholding the offending drugs. Proton-pump inhibitors appear to heal ulcers at the same rate whether or not NSAID therapy is continued. After the ulcer is healed and if NSAID therapy must be continued, prophylaxis is accomplished best by the concomitant use of proton-pump inhibitors, misoprostol (at least 200 micrograms 3 times a day), or a NSAID that preferentially inhibits COX-2. The future development of newer, safer NSAID preparations, including highly selective COX-2 inhibitors and nitric oxide-releasing NSAIDs, should provide better treatment options for the increasing number of individuals requiring anti-inflammatory agents.     

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs, including COX-2 selective drugs, are often used for acute and chronic musculoskeletal pain,including osteoarthritis, trauma, overuse syndromes, and compression fractures. Although these medications are often well tolerated in the young and otherwise healthy patient, the chronic use of these medications can lead to multiple medical problems, most commonly related to the gastrointestinal tract. Recently, concerns about cardiovascular adverse effects have been raised, particularly in the COX-2 drugs. Dosing and duration of therapy should be adjusted for comorbidities. CBC and renal and hepatic function should be checked at intervals of 3 to 6 months, depending on the patient.     

非甾体抗炎药的再认识

从第一个非甾体抗炎药（nonsteroidal antiinflammatory drugs,NSAIDs）阿司匹林问世,NSAIDs已有百余年历史。现已广泛应用于治疗各种风湿性疾病、心脑血管疾病。与NSAIDs相关的重要历史事件包括：20世纪70年代john Vane发现NSAIDs通过抑制环氧化酶（cyclooxygenase,cox）发挥抗炎镇痛作用,     

Nephrotoxicity of nonsteroidal anti-inflammatory drugs

Most nonsteroidal anti-inflammatory drugs can cause a variety of adverse renal effects when used in therapeutic doses. These effects range from elevation of BUN and creatinine to renal failure. Prostaglandin inhibition and T-lymphocyte disorder are believed to be the pathogenic factors. The effects are generally reversible with discontinuance of the drug, but some patients may require supportive management with hemodialysis and therapy with immunosuppressive agents.     

Nephrotoxicity from nonsteroidal anti-inflammatory drugs

We categorize the three types of renal dysfunction associated with the use of nonsteroidal anti-inflammatory drugs (NSAID): acute renal failure, acute interstitial nephritis, and hyperkalemia. The paper provides clinical examples of each type, discusses pathophysiology, and describes response to therapy, in addition to outlining the usefulness of labeled leukocyte nuclear studies and kidney biopsy. We conclude that these drugs are relatively common causes of renal dysfunction, particularly in selected subpopulations.