Increased reactive oxygen species (ROS) generation in diabetes mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy. Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an antioxidant agent by inhibiting NADPH oxidase activity and improving ROS scavenging. This study analyzed the influence of apocynin on cardiac remodeling in diabetic rats.
Six-month-old male Wistar rats were assigned into 4 groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was initiated and maintained for 8 weeks. Left ventricular (LV) histological sections were used to analyze interstitial collagen fraction. NADPH oxidase activity was evaluated in LV samples. Comparisons between groups were performed by ANOVA for a 2 × 2 factorial design followed by the Bonferroni post hoc test.
Body weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed by BW in both diabetic groups; apocynin did not affect these indices. LV systolic function was impaired in DM groups and unchanged by apocynin. Isovolumic relaxation time was increased in DM groups; transmitral E/A ratio was higher in DM + APO compared to DM. Myocardial functional evaluation through papillary muscle preparations showed impaired contractile and relaxation function in both DM groups at baseline conditions. After positive inotropic stimulation, developed tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those in DM and CTL + APO and did not significantly differ from either group. Myocardial interstitial collagen fraction was higher in DM than CTL and did not differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH oxidase activity did not differ between groups.
Apocynin restores serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase activity in diabetic rats.
Liu JJ, Lu Y, Ping NN, Li X, Lin YX, Li CF. Apocynin ameliorates pressure overload-induced cardiac remodeling by inhibiting oxidative stress and apoptosis. Physiol Res. 2017;66:741–52. PubMed
Thandavarayan RA, Watanabe K, Ma M, Gurusamy N, Veeraveedu PT, Konishi T, Zhang S, Muslin AJ, Kodama M, Aizawa Y. Dominant-negative p38alpha mitogen-activated protein kinase prevents cardiac apoptosis and remodeling after streptozotocin-induced diabetes mellitus. Am J Physiol Heart Circ Physiol. 2009;297:H911–9. CrossRefPubMed
Rosa CM, Gimenes R, Campos DH, Guirado GN, Gimenes C, Fernandes AA, Cicogna AC, Queiroz RM, Falcão-Pires I, Miranda-Silva D, et al. Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus. Cardiovasc Diabetol. 2016;15:126. CrossRefPubMedPubMedCentral
Gimenes C, Gimenes R, Rosa CM, Xavier NP, Campos DHS, Fernandes AAH, Cezar MDM, Guirado GN, Cicogna AC, Takamoto AHR, et al. Low intensity physical exercise attenuates cardiac remodeling and myocardial oxidative stress and dysfunction in diabetic rats. J Diabetes Res. 2015:ID 457848.
Rosa CM, Xavier NP, Campos DH, Fernandes AA, Cezar MD, Martinez PF, Cicogna AC, Gimenes C, Gimenes R, Okoshi MP, et al. Diabetes mellitus activated fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats. Cardiovasc Diabetol. 2013;12:152. CrossRefPubMedPubMedCentral
Lu J, Pontre B, Pickup S, Choong SY, Li M, Xu H, Gamble GD, Phillips AR, Cowan BR, Young AA, et al. Treatment with a copper-selective chelator causes substantive improvement in cardiac function of diabetic rats with left-ventricular impairment. Cardiovasc Diabetol. 2013;12:28. CrossRefPubMedPubMedCentral
Martinez PF, Okoshi K, Zornoff LA, Carvalho RF, Oliveira Junior SA, Lima AR, Campos DH, Damatto RL, Nogueira CR, Dal Pai-Silva M, et al. Chronic heart failure-induced skeletal muscle atrophy, necrosis, and myogenic regulatory factors changes. Med Sci Monit. 2010;16:374–83.
Oliveira Junior SA, Dal Pai-Silva M, Martinez PF, Lima-Leopoldo AP, Campos DH, Leopoldo AS, Okoshi MP, Okoshi K, Padovani CR, Cicogna AC. Diet-induced obesity causes metabolic, endocrine and cardiac alterations in spontaneously hypertensive rats. Med Sci Monit. 2010;16:BR367–73. PubMed
Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and The European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16:233–70. CrossRefPubMed
Gomes MJ, Martinez PF, Campos DHS, Pagan LU, Bonomo C, Lima AR, Damatto RL, Cezar MD, Damatto FC, Rosa CM, et al. Beneficial effects of physical exercise on functional capacity and skeletal muscle oxidative stress in rats with aortic stenosis-induced heart failure. Oxid Med Cell Longev. 2016;2016:8695716. CrossRefPubMedPubMedCentral
Cezar MD, Damatto RL, Pagan LU, Lima AR, Martinez PF, Bonomo C, Rosa CM, Campos DH, Cicogna AC, Gomes MJ, et al. Early spironolactone treatment attenuates heart failure development by improving myocardial function and reducing fibrosis in spontaneously hypertensive rats. Cell Physiol Biochem. 2015;36:1453–66. CrossRefPubMed
Habibi J, Aroor AR, Sowers JR, Jia G, Hayden MR, Garro M, Barron B, Mayoux E, Rector RS, Whaley-Connell A, et al. Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes. Cardiovasc Diabetol. 2017;16:9. CrossRefPubMedPubMedCentral
Prakoso D, De Blasio MJ, Qin C, Rosli S, Kiriazis H, Qian H, Du XJ, Weeks KL, Gregorevic P, McMullen JR, et al. Phosphoinositide 3-kinase (p110α) gene delivery limits diabetes-induced cardiac NADPH oxidase and cardiomyopathy in a mouse model with established diastolic dysfunction. Clin Sci. 2017;131:1345–60. CrossRefPubMed
- Influence of apocynin on cardiac remodeling in rats with streptozotocin-induced diabetes mellitus
C. M. Rosa
N. P. Xavier
D. H. S. Campos
A. A. H. Fernandes
M. D. M. Cezar
G. N. Guirado
L. U. Pagan
I. D. Chaer
D. C. Fernandes
F. R. Laurindo
A. C. Cicogna
M. P. Okoshi
- BioMed Central
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