Protective Effects of Rifampicin and Its Analog Rifampicin Quinone in a Mouse Model of Obesity-Induced Type 2 Diabetes

Advanced glycation end-products (AGEs) form when glucose
reacts
non-enzymatically with proteins, leading to abnormal protein function,
oxidative stress, and inflammation. AGEs are associated with aging
and age-related diseases; their formation is aggravated during diabetes.
Therefore, drugs preventing AGE formation can potentially treat diabetic
complications, positively affecting health. Earlier, we demonstrated
that rifampicin and its analogs have potent anti-glycating activities
and increase the life span of Caenorhabditis elegans. This study aimed to investigate the effects of rifampicin during
hyperglycemia in C. elegans and in
a mouse model of obesity-induced type 2 diabetes. The effects of rifampicin
were assessed by determining the life span of C. elegans cultured in the presence of glucose and by measuring HbA1c, AGE
levels, and glucose excursions in the diabetic mouse model. Our results
show that rifampicin protects C. elegans from glucose-induced toxicity and increases life span. In mice,
rifampicin reduces HbA1c and AGEs, improves insulin sensitivity, and
reduces indications of diabetic nephropathy without inducing hepatotoxicity.
Rifampicin quinone, an analog with lower anti-microbial activity,
also reduces HbA1c levels, improves glucose homeostasis and insulin
sensitivity, and lowers indications of diabetic nephropathy, without
adversely affecting the liver of the diabetic mice. Altogether, our
results indicate that rifampicin and its analog have protective roles
during diabetes without inflicting hepatic damage and may potentially
be considered for repositioning to treat hyperglycemia-related complications
in patients.