Schisandrin B Enhances Renal Mitochondrial Antioxidant Status, Functional and Structural Integrity, and Protects against Gentamicin-Induced Nephrotoxicity in Rats.
Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to protect against oxidative damage in liver, heart and brain tissues in rodents. In the present study, the effect of long-term Sch B treatment (1-10 mg/kg/d x 15) on gentamicin-induced nephrotoxicity was examined in rats. Sch B treatment protected against gentamicin-induced nephrotoxicity, as evidenced by significant decreases in plasma creatinine and blood urea nitrogen levels. The nephroprotection was associated with the enhancement in renal mitochondrial antioxidant status, as assessed by the level/activity of reduced glutathione, alpha-tocopherol and Mn-superoxide dismutase, as well as the improvement/preservation of mitochondrial functional and structural integrity, as assessed by the extents of ATP generation capacity, malondialdehyde production, Ca2+ loading and cytochrome c release, as well as the sensitivity to Ca2+-induced permeability transition, in control and gentamicin-intoxicated rats. In conclusion, long-term Sch B treatment could enhance renal mitochondrial antioxidant status as well as improve mitochondrial functional and structural integrity, thereby protecting against gentamicin nephrotoxicity.
Chiu
Po Yee
PY
Department of Biochemistry, The Hong Kong University of Science and Technology, Hong Kong SAR, China.
Leung
Hoi Yan
HY
Ko
Kam Ming
KM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism; D034242:Cyclooctanes / Q000494:pharmacology; D005260:Female; D005839:Gentamicins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D017705:Lignans / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D034242:Cyclooctanes; D005839:Gentamicins; D017705:Lignans; D011083:Polycyclic Compounds; C015499:schizandrin B; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D005978:Glutathione; D001205:Ascorbic Acid