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Protective effects of an aged garlic extract on the cardiotoxicity of doxorubicin (DOX) was evaluated using the mouse. DOX (1.5 mg/kg body wt i.p.) was administered three times per week for 40 days. An aged garlic extract, WG-1 (a preserved stock solution; Wakunaga Pharmaceutical) was administered intraperitoneally six times weekly. DOX caused changes in the electrocardiogram. In the control mice, the width of the QRS complex was 20 +/- 2.8 milliseconds, the R-R interval was 130 +/- 2.8 milliseconds, and the P-Q interval was 30 +/- 1.4 milliseconds. In mice treated with DOX for 40 days, the width of the QRS complex was 50 +/- 10 milliseconds (p < 0.05), the R-R interval was 240 +/- 30 milliseconds (p < 0.05), and the P-Q interval was 45 +/- 1.0 milliseconds (p < 0.01). These values were significantly smaller in mice treated with WG-1 + DOX than in mice treated with DOX. The width of the QRS complex was 29.3 +/- 5.8 milliseconds (p < 0.05), the R-R interval was 145.8 +/- 17.9 milliseconds (p < 0.01), and the P-Q interval was 37.8 +/- 3.5 milliseconds (p < 0.05). The lipid peroxidation in the heart homogenates prepared from DOX-treated mice, as measured by thiobarbituric acid-reactive substance (TBARS, nmol malondialdehyde/100 mg protein) was 332.5 +/- 67.0, which was significantly larger than that in the control mice (186.6 +/- 42.2) (p < 0.05). WG-1 decreased the level of TBARS in DOX-treated mice significantly. In the mice treated with WG-1 + DOX, TBARS was 221.3 +/- 31.6, which was significantly smaller than that of DOX-treated mice (p < 0.05). Histological study demonstrated that the heart treated with DOX had vacuolization in muscle cells, disrupted myofibrils, and swollen mitochondria. Mice that received WG-1 + DOX had no significant pathological lesions in the heart.

The effects of a protein-restricted diet on renal recovery following renal ischemia were studied. The renal function was assessed by measuring the inulin clearance (CIN), the p-aminohippurate clearance (CPAH), and the percent fractional sodium excretion (%FENa) 24 h after 45 min renal ischemia. In rats fed with a regular diet (containing 19.6% protein), CIN was 10.0 +/- 2.2 microL/min/100 g body weight (BW), CPAH 0.08 +/- 0.02 mL/min/100 g BW, and %FENa 14.8 +/- 2.0, 24 h after renal ischemia. In contrast, feeding rats with a no-protein diet (0% protein) for 1 week prior to the ischemic insult significantly improved renal recovery (CIN 48.0 +/- 9.3 microL/min/100 g BW, CPAH 0.16 +/- 0.04 mL/min/100 g BW, and %FENa 2.43 +/- 0.58). Feeding rats with a no-protein diet for 3 weeks prior to ischemic insult further improved the renal recovery (CIN 113 +/- 30 microL/min/100 g BW, CPAH 0.47 +/- 0.17 mL/min/100 g BW, and %FENa 1.55 +/- 0.29). When rats fed with a regular diet were exposed to 45 min of ischemia, the survival rate on day 7 was 16.7%. In rats fed with the no-protein diet for 1 week and for 3 weeks, the 7-day survival rate was 100% in each case. The survival rate of rats fed for 3 days instead of 7 days with the no-protein diet was 87.5%. When a no-protein feeding was shortened to 1 day, no beneficial effects were observed and survival rate was 14.3%. (ABSTRACT TRUNCATED AT 250 WORDS)