TABLE 5

Effects of a superoxide anion scavenger (tempol), a nonselective NOS inhibitor (l-NAME), a specific iNOS inhibitor (1400W), and a peroxynitrite scavenger (uric acid) on ethanol-induced mtDNA depletion in WT and MnSOD^+/− mice

Mice killed 2 or 24 h after the intragastric administration of water served as pooled zero-time controls (0 h) for the alcohol treatment. Other mice were killed 2 or 24 h after the intragastric administration of alcohol (5 g/kg). Thirty minutes before ethanol, some mice received an intraperitoneal injection of tempol (200 mg/kg b.wt.), l-NAME (80 mg/kg b.wt.), 1400 W (10 mg/kg b.wt.), or uric acid (500 mg/kg b.wt.). In mice that were sacrificed 24 h after ethanol administration, a second injection of the cotreatment was administered 8 h after ethanol administration. Values represent means ± S.E.M. for 5 to 18 mice. Two-way ANOVA indicated a global effect of genotype or treatment time or a significant interaction between genotype and treatment time (P < 0.05, two-way ANOVA).

Cotreatment	mtDNA/nDNA Hybridization Ratio in WT Mice			mtDNA/nDNA Hybridization Ratio in MnSOD^+/− Mice
Cotreatment	0 h	2 h	24 h	0 h	2 h	24 h
	% untreated WT mice
None	100 ± 4	64 ± 4^#	103 ± 5	101 ± 2	44 ± 4^#,*	67 ± 4^#,*
Tempol	102 ± 7	97 ± 10^†	94 ± 7	98 ± 7	102 ± 11^†	72 ± 9^#,*^,†
l-NAME	99 ± 3	85 ± 5^{^#,†}	111 ± 4	99 ± 3	78 ± 4^#,*^,†	93 ± 2^†
1400W	105 ± 11	99 ± 10^†	94 ± 9	106 ± 9	88 ± 8^†	103 ± 10^†
Uric acid	99 ± 3	96 ± 3^†	97 ± 4	91 ± 4	76 ± 3^#,*^,†	96 ± 3^#,*^,†

↵# Different from untreated mice (0 h) of the same genotype receiving the same cotreatment, if any (P < 0.05, two-way ANOVA).
↵* Different from WT mice studied at the same treatment time (0, 2, or 24 h) and receiving the same cotreatment, if any (P < 0.05, two-way ANOVA).
↵† Different from mice of the same genotype studied at the same treatment time but without any cotreatment (P < 0.05, one-way ANOVA within the WT group or within the MnSOD^+/− group).