Ageing involves oxidative stress mediated by
Reactive Oxygen Species (ROS) and
mitochondrial dysfunction. The present work demonstrates the protective effect of PQQ producing
EcN against
rotenone induced mitochondrial oxidative stress and consequence of mitochondrial and cellular dysfunction in naturally ageing rat model. PQQ is a potent
antioxidant molecule also known to stimulate mitochondrial biogenesis and function in mammals.
METHODS: Firstly, adult rats (16-18 weeks old) were treated with
rotenone (2.5 mg/kg
body weight; i.p.) daily for 28 days along with PQQ (10 mg/kg diet, daily) and modified probiotic
EcN strains (10(8) CFU twice weekly). Secondly, ageing rats (48-50 weeks old) were gavaged with probiotic
EcN strains (10(8)CFU twice weekly) and PQQ (10 mg/kg diet, daily) for 8 months.
RESULTS: PQQ producing EcN-5 treatment prevented
rotenone induced hepatic oxidative stress and mitochondrial damage in rats as assessed by reduced lipid peroxidation (29%), elevated
glutathione (GSH) content (43%), increased
catalase (52%) and
superoxide dismutase (52%) activities when compared to only
rotenone treatment. Moreover, increased hepatic mitochondrial content (41%),
peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α)
mRNA (25%) and mitochondrial
Superoxide Dismutase (Mit-SOD) activity (94%) were also observed in EcN-5 treated rats.
Rotenone treated rats did not exhibit gain in
body weight, whereas rats co-treated with EcN-5 showed significant restoration in
body weight gain. Furthermore, weekly administration of EcN-5 to naturally ageing rats for eight months resulted in significant reduction of oxidative stress in hepatic and colonic tissues (assessed by lipid peroxidation, GSH content and
catalase and SOD
enzyme activities) along with increase in hepatic mitochondrial
enzyme activities (Mit-SOD and
succinate dehydrogenase) and biogenesis, when compared to untreated rats. Additionally, these rats also exhibited reduced expression of
fatty acid synthase (50%) and increased expression of acyl
coenzyme oxidase (225%) genes in liver in contrast to untreated rats resulting in lowered
triglyceride (13% & 13.5%) and
cholesterol (21% & 27%) levels in plasma and liver, respectively. Increased levels of
butyrate (93%),
propionate (45%) and
acetate (18%) were also found in colonic content of these rats. PQQ administered daily (supplemented in diet) exhibited more or less similar effect as weekly gavaged EcN-5 in both the experiments, which substantiate that these effects are mediated by PQQ.
CONCLUSION: These results suggest that genetically modified EcN-5 can be used as a nutritional supplement which can reduce age related oxidative stress and
hyperlipidemia. Furthermore, it also rejuvenates healthy mitochondria by stimulating mitochondrial biogenesis and metabolism.