Possible involvement of long chain fatty acids in the spores of Ganoderma lucidum (Reishi Houshi) to its anti-tumor activity

During our isolation of biologically active substances from the spores of Ganoderma lucidum (Reishi Houshi, G. lucidum) guided by the inhibitory activity on HL-60 cell proliferation, NMR spectroscopic and mass spectrometric data indicate the substance contains a mixture of several long chain fatty acids. Hence, in this study, we have examined the inhibitory effects of an ethanolic extract of the spores of G. lucidum as the spore extract, on the proliferation of various human cancer cell lines by comparison with several authentic long chain fatty acids. Of the fatty acids we examined nonadecanoic acid (C19:0) showed the highest inhibitory activity for HL-60 cell proliferation with IC(50) values of 68+/-7 microM followed by heptadecanoic acid (C17:0, 120+/-23 microM), octa- (C18:0, 127+/-4 microM) and hexadecanoic acids (C16:0, 132+/-25 microM), respectively. The corresponding unsaturated fatty acids containing one double bond such as cis-10-nonadecenoic acid (C19:1), cis-9-octadecenoic acid (C18:1), cis-10-heptadecenoic acid (C17:1) and cis-9-hexadecenoic acid (C16:1) were less effective. The ethanolic extract of spores of G. lucidum were shown by annexin-V FITC/PI double staining to induce apoptosis of HL-60 cells in a similar way to cis-10-nonadecenoic acid (C19:1). These unsaturated fatty acids probably inhibit tumor necrosis factor production induced by lipopolysaccharide in a mouse macrophage preparation. Our results suggest the spores of G. lucidum contain 19-carbon fatty acids as one of the components for characteristics of its physiological effects.     

The determination of glycyrrhizic acid in Glycyrrhiza uralensis Fisch. ex DC. (Zhi Gan Cao) root and the dried aqueous extract by LC-DAD

A rapid, sensitive and specific reversed phase high-performance liquid chromatographic (LC) method with photodiode array detection (DAD) has been developed for the determination of glycyrrhizic acid in both the raw herb and a commercially prepared dried aqueous extract of Glycyrrhiza uralensis Fisch. ex DC. root (Zhi Gan Cao, liquorice). It was determined that extracting the raw herb in aqueous methanol (50:50 v/v) by sonication for 2 x 30 min was the most efficient sample preparation. Baseline resolution of the glycyrrhizic acid peak was achieved on a Varian Polaris RP C18-A (250 mm x 4.6 mm, 5 microm packing) column using an isocratic mobile phase consisting of 0. v aqueous phosphoric acid and acetonitrile in the ratio 60:40 v/v. Chromatograms were monitored between 200 and 400 nm for peak purity assessments, with quantitation performed at 254 nm. Glycyrrhizic acid calibration curves in the concentration range of 14-558 microg/ml were prepared on the day of analysis. Curve fitting was by the least-squares method, with correlation coefficients of >0.9998 obtained each time. The average recovery at three spike levels (50, 100, 200%) was of 95.91+/-1.05% and 98.36+/-3.45% (+/-S.D., n=7) for the spiked raw herb and dried aqueous extract respectively. The limit of detection and limit of quantitation was 0.52 and 1.72 mg/g respectively for the raw herb, and 0.75 and 2.51 mg/g respectively for the dried aqueous extract. Identity confirmation of the chromatographic peak was achieved by (-) electrospray ionisation tandem mass spectrometry. The concentration of glycyrrhizic acid in the root and dried aqueous extract was found to be 31.1+/-0.2 and 40.4+/-0.3mg/g (+/-S.D., n=7) respectively.     

Differential modulation by simvastatin of the metabolic pathways in the n-9, n-6 and n-3 fatty acid series, in human monocytic and hepatocytic cell lines

Statins affect the production of long chain polyunsaturated fatty acids (PUFA), both in vitro and in vivo. Various studies have shown the effects of statins on the pattern of n-6 fatty acids (FA), but limited attention has been paid to the n-3 FA. We investigated, in THP-1 and in HepG2 cells, the effects of simvastatin on the conversion of the 18C FA precursors in the n-3 and n-6 series, [1-(14)C] alpha-linolenic acid (alpha-LNA) and [1-(14)C] linoleic acid (LA) respectively, and on the metabolism of [1-(14)C] stearic acid (SA). THP-1 cells, as in the case of LA, actively converted alpha-LNA to its products, and after simvastatin treatment, the total conversion was significantly increased (from 57.2+/-7.2 to 74.3+/-8.5%, p<0.05). HepG2 cells also converted LA and alpha-LNA, but simvastatin increased significantly only the conversion of LA (9.5+/-1.9% versus 23.8+/-5.1%, p<0.02). SA conversion was similar in untreated cells (about 50%), while statin increased the production of oleic acid in HepG2, but in THP-1 cells there was a decrease. In conclusion, LA, alpha-LNA and SA are differentially metabolized in THP-1 and in HepG2 cells and their increased conversion by simvastatin is lower in HepG2 than in THP-1. These differences may reflect the distinct features of the two cell lines: monocytes, precursors of phagocytic cells, versus hepatocytes with mainly metabolic functions. Substantial differences concern also cellular FA pools: structural in THP-1 cells, and also depot, resulting in sequestering of the substrates, in HepG2. The greater n-3 FA metabolism in THP-1 cells may have favourable functional effects.     

中药红曲中氨基酸和脂肪酸的分析

目的：考察中药红曲中氨基酸和脂肪酸的含存情况。方法：采用氨基酸自动分析仪进行氨基酸的分析,采用气相色谱仪进行脂肪酸的分析。结果：国内8个产地及自制新红白H18中含有19种氨基酸,其中有10种药用氨基酸（48％～63％）,7种人体必需氨基酸（29％～45％）,游离氨基酸的含量（0．81％～1．14％）约为其发酵培养基粳米的15倍～21倍。国内8个产地红曲中多烯不饱和脂肪酸约为总脂肪酸的16％～27％,而新红白H18中多烯不饱和脂肪酸约为总脂肪酸的48％。结论：红曲中富含有多种游离氨基酸及多烯不饱和脂肪酸,新红曲H18与各地产红曲在脂肪酸化学成分的相对百分含量上有较大区别。提示,新红曲H18的产生菌株与各地红曲的原始菌株可能不是同一种或是其一变种。     

Antinociceptive, antiinflammatory and antipyretic properties of Channa striatus fillet aqueous and lipid-based extracts in rats

The present study was carried out to elucidate the antinociceptive, antiinflammatory and antipyretic properties of the aqueous and lipid-based extracts of Channa striatus fillet in rats. The antinociceptive activity was assessed using the formalin test, and the antiinflammatory and antipyretic activities were assessed using the carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. Both types of extracts were prepared in concentrations of 10%, 50% and 100% by serial dilution in distilled water or dimethyl sulfoxide, respectively, and were administered subcutaneously 30 min prior to each test. Except for the 10% aqueous extract which exhibits activity only in the early phase, the extracts were found to exhibit significant (P < 0.05) activity in the early and late phases of the formalin test. Furthermore, the aqueous and lipid-based extracts were also found to show significant (P < 0.05) antiinflammatory activity, with the former showing a greater effect at the lowest concentration used. The lipidbased, but not the aqueous, extract was found to have significant (P < 0.05) activity in the pyrexia test. In conclusion, the present study demonstrated that C. striatus extracts possess antinociceptive, antiinflammatory and antipyretic activities.     

Fatty acids in Botryococcus braunii accelerate topical delivery of flurbiprofen into and across skin

To improve the drug absorption into and across the skin, fatty acids extracted from Botryococcus braunii were evaluated using in vitro and in vivo techniques with Wistar rats as the animal model. Palmitic acid (C16:0), oleic acid (C18:1), linoleic acid (C18:2), and linolenic acid (C18:3) were the major components in the B. braunii extract. Topical delivery of flurbiprofen was significantly enhanced after pretreatment with 3% B. braunii extract for 30min in an in vitro Franz cell and in vivo pharmacokinetic studies. Pure unsaturated fatty acids were more-effective enhancers than the B. braunii extract. However, a greater irritant potential was also observed with those fatty acids than with the B. braunii extract according to the skin tolerance study as determined by transepidermal water loss (TEWL). Both human keratinocytes and skin fibroblasts showed a 1.5-2-fold increase in prostaglandin E(2) (PGE(2)) release as compared to the control. The findings in this study indicate that the fatty acids in B. braunii may be useful enhancers for flurbiprofen delivery via the skin.     

Skin Permeation Enhancement of Diclofenac by Fatty Acids

This study systematically investigated the enhancing effect of fatty acids on the skin permeation of diclofenac. The fatty acids were evaluated in terms of their carbon-chain length, the degree of unsaturation, and their functional groups. The rat-skin permeation rates of diclofenac, saturated in propylene glycol (PG) containing 1% (w/v) fatty acid, were determined using the Keshary-Chien diffusion cells at 37°C. The effect of fatty acids on the saturated solubility of diclofenac in PG was also determined at 37°C using high-performance liquid chromatography. Among the saturated fatty acids tested, palmitic acid (C16:0) showed the most potent skin permeation-enhancing effect. A parabolic correlation was observed between the enhancement effect and the fatty acid carbon-chain length among these saturated fatty acids of C12–C20 units. For the monounsaturated fatty acid series, an increase in permeation was observed as the carbon-chain length increased, and oleic acid (C18:1) showed the highest permeation-enhancing effect. Increasing the number of double bonds in the octadecanoic acids resulted in a parabolic effect in the permeation of diclofenac, revealing oleic acid as the most effective enhancer used in this study. When the carboxylic acid moiety of oleic acid was changed to an amide (oleamide) or hydroxyl (oleyl alcohol) group, a decrease in permeation activity was observed. These results, therefore, suggest that the cis-monounsaturated configuration and the carboxylic acid moiety of an 18-carbon unit fatty acid in PG are the optimum requirements for the effective skin permeation of diclofenac.     

三化汤对缺血性中风模型大鼠血清脂肪酸谱的影响

目的:观察三化汤对缺血性中风模型大鼠血清脂肪酸谱的影响.方法:采用线栓法建立大鼠大脑中动脉阻塞模型(MCAO模型),随机分为模型组、干预组,每组10只.另设正常组、假手术组,每组各10只.正常组、假手术组、模型组灌胃纯净水,干预组灌胃三化汤水煎液,连续给药10 d.10 d后处死大鼠,取血清样本,采用气相色谱-质谱联用...     

卤虫中蛋白质和脂肪酸组成的研究

用毛细管气相色谱法、微量凯氏定氮法、氨基酸自动分析仪对卤虫中蛋白质和脂肪酸组成进行分析。结果表明，蛋白质含量比较高，富含18种氨基酸，包括8种必需氨基酸。色谱分离出32个峰。主要脂肪酸有C16：1（n－7），17．3％；C18：1（n－9），20％；C18：2（n－6），2．8％；C18：3（n－3），2．5％；C20：5（n-3），3．5％。     

Soraphen A, an inhibitor of acetyl CoA carboxylase activity, interferes with fatty acid elongation

Acetyl CoA carboxylase (ACC1 and ACC2) generates malonyl CoA, a substrate for de novo lipogenesis (DNL) and an inhibitor of mitochondrial fatty acid β-oxidation (FAO). Malonyl CoA is also a substrate for microsomal fatty acid elongation, an important pathway for saturated (SFA), mono- (MUFA) and polyunsaturated fatty acid (PUFA) synthesis. Despite the interest in ACC as a target for obesity and cancer therapy, little attention has been given to the role ACC plays in long chain fatty acid synthesis. This report examines the effect of pharmacological inhibition of ACC on DNL and palmitate (16:0) and linoleate (18:2, n − 6) metabolism in HepG2 and LnCap cells. The ACC inhibitor, soraphen A, lowers cellular malonyl CoA, attenuates DNL and the formation of fatty acid elongation products derived from exogenous fatty acids, i.e., 16:0 and 18:2, n − 6; IC₅₀ ∼ 5 nM. Elevated expression of fatty acid elongases (Elovl5, Elovl6) or desaturases (FADS1, FADS2) failed to override the soraphen A effect on SFA, MUFA or PUFA synthesis. Inhibition of fatty acid elongation leads to the accumulation of 16- and 18-carbon unsaturated fatty acids derived from 16:0 and 18:2, n − 6, respectively. Pharmacological inhibition of ACC activity will not only attenuate DNL and induce FAO, but will also attenuate the synthesis of very long chain saturated, mono- and polyunsaturated fatty acids.     

北沙参的脂肪酸特征及产地差异性分析

目的 研究北沙参的脂肪酸特征,比较山东莱阳、河北安国、内蒙古赤峰等三个主产地的北沙参脂肪酸差异。方法 Bligh and Dyer法提取总脂;甲酯化后,利用气相色谱-质谱联用仪（GC-MS）分析;通过与脂肪酸标准品及NIST 11.0质谱数据库比对鉴定脂肪酸种类,采用面积归一法分别计算各成分的相对质量分数。结果 分别从山东莱阳、河北安国和内蒙古赤峰的北沙参药材中鉴定了17、17和18种脂肪酸;三个产地药材的优势脂肪酸种类一致,依次为C18:2 n-6c（亚油酸,49.22~63.96%）、C16:0（棕榈酸,17.43~25.33%）和C18:1 n-9c（油酸,13.85~19.44%）,均未检测到n-3型多不饱和脂肪酸（PUFA）。山东莱阳药材的多不饱和脂肪酸总量（PUFA）低于河北安国及内蒙古赤峰,但饱和脂肪酸（SFA）、 单不饱和脂肪酸（MUFA）和多不饱和脂肪酸（PUFA）三者比值最接近1:1:1。结论 不同产地北沙参的脂肪酸种类相近。亚油酸是北沙参含量优势脂肪酸,提示可以作为北沙参防治胆固醇代谢相关疾病的质量标志物候选分子。     

建立UPLC法测定复方氨基酸胶囊(9-5)中氨基酸的含量

目的通过优化色谱条件建立UPLC法测定复方氨基酸胶囊(9-5)中氨基酸的含量。方法以9种氨基酸对照为外标物,异硫氰酸苯酯为柱前衍生剂,采用ACQUITY UPLCBEH C_(18)(2.1 mm×100 mm,1.7μm)柱,流动相A为0.1 mol/L的醋酸钠溶液(用冰醋酸调整pH至6.50)-乙腈(93∶7),流动相B为乙腈-水(4∶1),检测波长254 nm,流速为0.45 mL/min,柱温36℃。结果复方氨基酸胶囊(9-5)中9种氨基酸出峰时间与对照品出峰时间一致,其他物质无干扰;仪器精密度RSD为0.5%~1.2%,中间精密度RSD为1.3%~1.9%;各氨基酸的溶液浓度与其峰面积线性关系良好(r≥0.999),溶液稳定性RSD为0.6%~1.8%,各氨基酸的平均回收率在95.0%~105.0%之间。含量测定方法比对实验中UPLC法与HPLC法分析结果无明显差异,分析速度明显提高。结论建立的UPLC法高效,快速,灵敏,准确,可用于测定复方氨基酸胶囊(9-5)中氨基酸的含量。     

Clofibric acid increases the formation of oleic acid in endoplasmic reticulum of the liver of rats

The effects of 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) on the formation of oleic acid (18:1) from stearic acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [1?C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) clofibric acid for 7 days; and the distribution of radiolabeled fatty acids among subcellular organelles, microsomes, peroxisomes, and mitochondria, was estimated on the basis of correction utilizing the yields from homogenates of marker enzymes for these organelles. The radioactivity was mostly localized in microsomes and the radiolabeled fatty acids present in microsomes were significantly increased by the treatment of rats with clofibric acid. The formation of radiolabeled 18:1 in microsomes markedly increased and incorporations of the formed [1?C]18:1 into PC and phosphatidylethanolamine in microsomes were augmented in response to clofibric acid. The [1?C]18:1 incorporated into PC was mostly located at the C-2 position, but not the C-1 position, of PC, and the radioactivity in 18:1 at the C-2 position of PC was strikingly increased by clofibric acid. These results obtained from the in vivo experiments directly link the findings that clofibric acid treatment induces microsomal stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase in the liver and the findings that the treatment with the drug elevated absolute mass and mass proportion of 18:1 at the C-2 position, but not the C-1 position, of PC in the liver together.     

家蚕氨基酸、微量元素及总黄酮含量测定分析

目的测定分析全蚕粉中营养成分及总黄酮含量,为家蚕保健食品和药物研究开发提供实验数据。方法采用高效液相色谱（HPLC）法,6-氨基喹啉-N-羟基琥珀酰亚氨基甲酸酯（AQC）为衍生剂,测定氨基酸含量。凯氏自动定氮仪测定蛋白质含量。索氏提取法提取蚕粉中总脂肪酸。原子吸收光谱法测定微量元素含量。紫外分光光度法测定总黄酮含量。结果全蚕粉含16种氨基酸,蛋白质含量高达60％,脂肪酸含量2％,微量元素含量较为丰富。总黄酮含量约为18mg／g。结论HPLC法测定氨基酸操作简便、衍生化反应彻底。家蚕营养成分、总黄酮含量高,确为药食两用佳品。     

Isolation of fatty acids with anticancer activity from<Emphasis Type="Italic">Protaetia brevitarsis</Emphasis> Larva

In this study, biologically active compounds were isolated from Protaetia brevitarsis larva (PBL) by dichloromethane extraction. The dichloromethane extract from PBL was highly cytotoxic to various cancer cells. From a silica gel column chromatograpy of this extract, we obtained four fractions (F-2, F-4, F-5 and F-7) having apoptosis-inducing activity. These fractions induced DNA ladder and caspase-3 activation during apoptosis in colon 26 tumor cells. In 1H and 13C NMR and mass spectral analysis of the fraction F-2 showing the highest apoptosis-inducing activity, we found that the fraction was composed of three free fatty acids such as palmitic acid, (Z)-9-octadecenoic acid and octadecenoic acid. These results indicate that the dichloromethane extract of PBL includes anticancer components composed of at least three fatty acids, and apoptosis-inducing activity of the extract was mediated by caspase-3 activation in tumor cells.     

Effects of various nonopioid receptor antagonists on the antinociceptive activity of Muntingia calabura extracts in mice

This study was carried out in mice to determine the nonopioid receptor signaling pathway(s) that might modulate the antinociceptive activity of the aqueous and chloroform extracts of Muntingia calabura (M. calabura) leaves, using the hot-plate test. The leaves of M. calabura were sequentially soaked [1:2 (w/v); 72 h] in distilled water (dH(2)O) and chloroform. The 50% concentration extracts were selected for this study based on the plant's previously established antinociceptive profiles. The mice (n = 7) were pretreated (s.c.) for 10 min with the selected nonopioid receptor antagonists, followed by the (s.c.) administration of the respective extract. The latency of discomfort was recorded at the interval time of 0.5, 1, 2, 3, 4 and 5 h after the extract administration. The 5 mg/kg atropine, 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol, 1 mg/kg haloperidol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the aqueous extract-induced antinociceptive activity. The 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the chloroform extract-induced antinociceptive activity. In conclusion, the central antinociceptive activity of M. calabura leaves appears to be involved in the modulation of various nonopioid receptor signaling pathways. Its aqueous extract antinociceptive activity is mediated via modulation of the muscarinic, alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic, dopaminergic and GABAergic receptors, while its chloroform extract activity is mediated via modulation of the alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic and GABAergic receptors.     

In vitro antioxidant capacities and fatty acid compositions of three Centaurea species collected from Central Anatolia region of Turkey

Antioxidant capacities of methanolic extract and fatty acid composition of three Centaurea species were investigated. The antioxidant capacity of the extracts was evaluated by different assays, including total phenolic content, phosphomolybdenum assay, free radical scavenging activity (DPPH assay), β-carotene/linoleic acid bleaching assay, iron (III) and cupric reduction assay. The findings showed that the methanolic extract of Centaurea pulchella has the strongest antioxidant capacity compared to other two Centaurea species. The order of the antioxidant properties of Centaurea species were C. pulchella > C. patula > C. tchihatcheffii. Thirty fatty acids were identified in the oils of three Centaurea species. The major fatty acids of these species were found to be linoleic acid from C. pulchella and C. tchihatcheffii, and α-linolenic acid from C. patula. The study concluded that the Centaurea species can be used as a source of natural antioxidants and essential fatty acids.     

不饱和脂肪酸对豚鼠胃窦环行肌细胞毒蕈碱电流的影响

目的：研究外源性不饱和脂肪酸对豚鼠胃窦平滑肌细胞素毒蕈碱电流的影响及其作用机制。方法：利用膜片箝技术的全细胞记录法在急性分离的胃窦环行肌细胞上记录毒蕈碱电流。结果：在细胞外灌流液中给予花生四烯酸（arachidonic acid,AA）明显抑制I_cch,并具有量效关系：当AA的浓度在1。3和μmo1/L时,分别抑制I_cch至46%±8%,23%±5%和3.8%±0.9%;另一种不饱和脂肪酸,亚麻酸（linoleic acid,LA）也抑制I_cch,在1,5和10μmo1/L浓度分别抑制I_cch至3.8%±0.9%,35%±5%和67%±9%;用H-7（蛋白激酶C抑制剂）100μmo1/L预处理10-15分钟以后,AA分别抑制I_cch至5.5%±0.7%和3.0%±1.0%。结论：不饱和脂肪酸直抑制毒蕈碱电流,且抑制程度与不饱和脂肪酸链中的双键数目有关。     

海参磷脂型EPA对血清及肝脏脂肪酸组成的改善作用

目的 本文研究了海参磷脂型EPA(Eicosapntemacnioc acid-enriched phosphatidylcholine from sea cucumber,EPA-PC) 对非酒精性脂肪肝(Nonalcoholic fatty live disease, NAFLD)大鼠血清和肝脏脂肪酸组成的改善作用。方法 以NAFLD大鼠为模型,灌胃EPA-PC 4w,检测血清中和肝脏中脂质水平及脂肪酸组成。结果 EPA-PC显著降低模型大鼠血清和肝脏总脂中甘油三酯(Triglyceride,TG)和总胆固醇(Total cholesterol,TC)水平,显著升高血清高密度脂蛋白(High density lipoprotein cholesterol,HDLC)/TC水平;显著升高血清和肝脏中多不饱和脂肪酸(Polyunsaturated fatty acids,PUFA)的比例,降低n6/n3PUFA比例,升高DHA比例,降低肝脏总脂和磷脂去饱和C18：1/C18：0指数的比例,改善脂肪酸组成。结论 EPA-PC可以使血清和肝脏脂质水平下降,改变血清和肝脏脂肪酸组成,使NAFLD大鼠脂质水平紊乱状态得到改进。     

Effect of gentamicin on lipid peroxidation in rat renal cortex

We examined the hypothesis that lipid peroxidation participates in the pathogenesis of aminoglycoside-induced nephrotoxicity. Male Sprague-Dawley rats were injected subcutaneously with gentamicin, 100 mg/kg per day, for 1-4 days. Twenty-four or forty-eight hours after the last injection the rats were killed and the renal cortex was processed for total phospholipids, malondialdehyde (MDA), phospholipid fatty acid composition, superoxide dismutase, catalase and glutathione. Gentamicin induced a significant increase in total renal cortical phospholipids which was evident after a single injection and by the third injection reached a plateau 17% above the baseline level. MDA, an end product of lipid peroxidation, increased from 0.674 +/- 0.021 nmole/mg protein in the control group to 0.931 +/- 0.053 nmole/mg protein (P less than 0.001) 48 hr after the fourth injection. As another index of lipid peroxidation, we determined the shift from polyunsaturated to saturated fatty acids of renal cortical phospholipids. By the second injection of gentamicin we detected a significant decline of arachidonic acid (20:4) present in phospholipid. By the fourth injection, arachidonic acid had fallen 48% below control and was accompanied by reciprocal increases of more saturated fatty acids including linoleic (18:2), oleic (18:1) and palmitic (16:0) acids. The number of double bonds per mole of fatty acid declined from a baseline value of 1.62 +/- 0.01 to 1.20 +/- 0.02 (P less than 0.001) by the fourth injection of drug. Superoxide dismutase showed no consistent alteration, whereas catalase activity (k) fell from the control value of 0.221 +/- 0.007 min to 0.155 +/- 0.009 min (P less than 0.01) by the third injection, where k is the first-order rate constant. Total and reduced glutathione declined after the fourth injection of gentamicin accompanied by a shift to oxidized glutathione with an increase in the ratio of oxidized to total glutathione. These data support the conclusion that accelerated lipid peroxidation occurs early in the course of gentamicin administration and raise the possibility that lipid peroxidation is a proximal event in the injury cascade of gentamicin nephrotoxicity.