thus appeared to cause differential inhibition of two forms of cytochrome P450, and
thus would accordingly affect the steady-state level of those drugs metabolized by
these pulmonary forms of cytochromes P450 (Reen and Singh 1991).
22.8 Effects on Antioxidant Pathways in Tissues
from Diabetic Rats
Excessive oxidative stress has been implicated in the pathology and complications
of diabetes mellitus (Matough et al. 2012), as well as other conditions including
cancer, multiple sclerosis, muscular dystrophy, emphysema, Parkinson’s disease,
Alzheimer’s disease, and the aging process (Kehrer and Klotz 2015).
Hyperglycemia generates abnormally high levels of free radicals by a mechanism
involving autoxidation of glucose, followed by oxidative degeneration and protein
glycation (Hunt et al. 1988). In addition, nonenzymatic glycosylation of those
enzymes that normally detoxify free radical species may exacerbate oxidative stress
in diabetes. Thus, clinical complications in diabetes and other oxidative
stress-related diseases may be due partially to the inability of key antioxidant
enzymes to function at normal levels (Karan et al. 2012; Pal et al. 2008; Pal 2013;
Rauscher et al. 2000).
Complications of diabetes mellitus, which include atherosclerosis, ischemic heart
disease, fatty liver, retinopathy, cataract, nephropathy, and neuropathy, are associated with oxidative modifications of various tissue components (Matough et al.
2012; Oberley 1988; Wolff 1993). In diabetes, cell death resulting from inflammation or oxidative damage may release products of protein catabolism, including
transition metals. These may serve to perpetuate the generation of reactive oxygen
species such as hydroxyl and superoxide radicals. The effects of diabetes on
antioxidant defense, consistent with those seen by other researchers, include alterations in detoxifying enzyme activity in every tissue studied, as well as increases in
hepatic lipid peroxidation and decreases in the hepatic concentration of GSH, an
endogenous free radical scavenger. In diabetic rats, piperine treatment resulted in the
reversal of diabetic effects on cardiac lipid peroxidation (the 33% reduction by
diabetes was returned to untreated normal values after piperine), on cardiac glutathione reductase activity (the 50% increase by diabetes was reduced to 25% above
untreated normal values after piperine), on renal glutathione peroxidase activity
(145% increase by diabetes was reversed to 52% above normal after piperine), and
on superoxide dismutase activity in kidney (the 90% increase by diabetes was
somewhat decreased after piperine). Likewise, piperine reversed the
diabetes-induced changes in the concentration of GSSG in brain (the 54% increase
by diabetes was decreased almost to untreated normal values after piperine). Piperine
treatment appeared to have no effect on hepatic TBA and GSH concentrations or
catalase or glutathione peroxidase activities or on cardiac catalase or glutathione
peroxidase activities that were altered by diabetes. The 19% increase in glutathione
764
N. Sachan et al.
thus would accordingly affect the steady-state level of those drugs metabolized by
these pulmonary forms of cytochromes P450 (Reen and Singh 1991).
22.8 Effects on Antioxidant Pathways in Tissues
from Diabetic Rats
Excessive oxidative stress has been implicated in the pathology and complications
of diabetes mellitus (Matough et al. 2012), as well as other conditions including
cancer, multiple sclerosis, muscular dystrophy, emphysema, Parkinson’s disease,
Alzheimer’s disease, and the aging process (Kehrer and Klotz 2015).
Hyperglycemia generates abnormally high levels of free radicals by a mechanism
involving autoxidation of glucose, followed by oxidative degeneration and protein
glycation (Hunt et al. 1988). In addition, nonenzymatic glycosylation of those
enzymes that normally detoxify free radical species may exacerbate oxidative stress
in diabetes. Thus, clinical complications in diabetes and other oxidative
stress-related diseases may be due partially to the inability of key antioxidant
enzymes to function at normal levels (Karan et al. 2012; Pal et al. 2008; Pal 2013;
Rauscher et al. 2000).
Complications of diabetes mellitus, which include atherosclerosis, ischemic heart
disease, fatty liver, retinopathy, cataract, nephropathy, and neuropathy, are associated with oxidative modifications of various tissue components (Matough et al.
2012; Oberley 1988; Wolff 1993). In diabetes, cell death resulting from inflammation or oxidative damage may release products of protein catabolism, including
transition metals. These may serve to perpetuate the generation of reactive oxygen
species such as hydroxyl and superoxide radicals. The effects of diabetes on
antioxidant defense, consistent with those seen by other researchers, include alterations in detoxifying enzyme activity in every tissue studied, as well as increases in
hepatic lipid peroxidation and decreases in the hepatic concentration of GSH, an
endogenous free radical scavenger. In diabetic rats, piperine treatment resulted in the
reversal of diabetic effects on cardiac lipid peroxidation (the 33% reduction by
diabetes was returned to untreated normal values after piperine), on cardiac glutathione reductase activity (the 50% increase by diabetes was reduced to 25% above
untreated normal values after piperine), on renal glutathione peroxidase activity
(145% increase by diabetes was reversed to 52% above normal after piperine), and
on superoxide dismutase activity in kidney (the 90% increase by diabetes was
somewhat decreased after piperine). Likewise, piperine reversed the
diabetes-induced changes in the concentration of GSSG in brain (the 54% increase
by diabetes was decreased almost to untreated normal values after piperine). Piperine
treatment appeared to have no effect on hepatic TBA and GSH concentrations or
catalase or glutathione peroxidase activities or on cardiac catalase or glutathione
peroxidase activities that were altered by diabetes. The 19% increase in glutathione
764
N. Sachan et al.