Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables

Natalia Jorgelina Prado; Daniela Ramirez; Luciana Mazzei; Micaela Parra; Mariana Casarotto; Juan Pablo Calvo; Darío Cuello Carrión; Amira Zulma Ponce Zumino; Emiliano Raúl Diez; Alejandra Camargo; Walter Manucha

doi:10.1016/j.heliyon.2022.e08989

Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables

Heliyon. 2022 Feb 17;8(2):e08989. doi: 10.1016/j.heliyon.2022.e08989. eCollection 2022 Feb.

Authors

Natalia Jorgelina Prado^{1

2}, Daniela Ramirez^{3

4}, Luciana Mazzei^{1

2}, Micaela Parra², Mariana Casarotto², Juan Pablo Calvo², Darío Cuello Carrión¹, Amira Zulma Ponce Zumino², Emiliano Raúl Diez^{1

2}, Alejandra Camargo^{3

4}, Walter Manucha^{1

2}

Affiliations

¹ Institute of Experimental Medicine and Biology of Cuyo (IMBECU)-UNCuyo-CONICET, Mendoza 5500, Argentina.
² Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza 5500, Argentina.
³ Instituto de Biología Agrícola de Mendoza, (IBAM), Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina.
⁴ Facultad de Ciencias Agrarias, Chacras de Coria, Mendoza, Argentina.

Abstract

Background: Cardiovascular inflammation and oxidative stress are determining factors in high blood pressure and arrhythmias. Indole-3-carbinol is a cruciferous-derived phytochemical with potential anti-inflammatory and antioxidant effects. However, its implications on the modulation of cardiovascular inflammatory-oxidative markers are unknown.

Objectives: To establish the effects of indole-3-carbinol on the oxidative-inflammatory-proarrhythmic conditions associated with hypertension.

Materials: Histological, biochemical, molecular, and functional aspects were evaluated in 1) Culture of mouse BV-2 glial cells subjected to oxidative-inflammatory damage by lipopolysaccharides (100 ng/mL) in the presence or absence of 40 μM indole-3-carbinol (n = 5); 2) Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats receiving indole-3-carbinol (2000 ppm/day, orally) during the first 8 weeks of life (n = 15); 3) Isolated rat hearts were submitted to 10 min regional ischemia and 10 min reperfusion.

Results: 1) lipopolysaccharides induced oxidative stress and increased inflammatory markers; indole-3-carbinol reversed both conditions (interleukin 6, tumor necrosis factor α, the activity of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide, inducible nitric oxide synthase, heat shock protein 70, all p < 0.01 vs lipopolysaccharides). 2) SHR rats showed histological, structural, and functional changes with increasing systolic blood pressure (154 ± 8 mmHg vs. 122 ± 7 mmHg in Wistar Kyoto rats, p < 0.01); Inflammatory-oxidative markers also increased, and nitric oxide and heat shock protein 70 decreased. Conversely, indole-3-carbinol reduced oxidative-inflammatory markers and systolic blood pressure (133 ± 8 mmHg, p < 0.01 vs. SHR). 3) indole-3-carbinol reduced reperfusion arrhythmias from 8/10 in SHR to 0/10 (p = 0.0007 by Fisher's exact test).

Conclusions: Indole-3-carbinol reduces the inflammatory-oxidative-proarrhythmic process of hypertension. The nitric oxide and heat shock protein 70 are relevant mechanisms of indole-3-carbinol protective actions. Further studies with this pleiotropic phytochemical as a promising cardioprotective are guaranteed.

Keywords: Arrhythmias; Hsp70; Hypertension; Indole-3-carbinol; Inflammation; Oxidative stress.