Therapeutic effect of bromelain and papain on intestinal injury induced by indomethacin in male rats

Abstract

Objectives: Inflammatory bowel diseases (IBDs) are a multiple inflammatory status in small intestines and colon. Bromelain and Papain were cysteine proteases enzymes extracted from pineapple and papaya, and possess antioxidant and anti-inflammatory characteristics. Therefore, this comparative work aimed to examine the anti-inflammatory and antioxidant effect of bromelain and papain in intestinal inflammation of rats and to evaluate the most potent effect of both types of enzymes.

Methods: Forty rats were used in this study (8 rats/group), G1: control group, G2: (Indo group) intestinal inflammation was induced by two doses of Indomethacin (7.5 mg/kg body weight) apart 24 h. G3: (Indomethacin + Bromelain) intestinal inflamed rats treated by oral dose of bromelain (1000 mg/kg/day). G4: (Indomethacin + Papain) intestinal inflamed rats treated by oral dose of papain (800 mg/kg/day). G5: (Indomethacin + Sulfasalazine) intestinal inflamed rats treated by oral dose of sulfasalazine (500 mg/kg/day). Oxidative stress and inflammatory markers were measured along with histological assessment.

Results: Indomethacin-induced intestinal inflammation (in both Jejunum and Ileum) characterized by increased oxidative stress biomarkers: Xanthine oxidase, Catalase, Glutathione reductase, and Protein carbonyl and Inflammatory biomarkers: Tumor necrosis factor-α, Interleukin-10, Monocyte chemoattractant protein-1, Nuclear factor-kappa β, C-reactive protein, and Prostaglandin E2, as compared to control rats. On the other hand, administering either bromelain or Papain would effectively decrease symptoms of intestinal inflammation and modulate biomarkers of oxidative stress and pro-inflammatory cytokines.

Conclusion: Comparing results revealed that bromelain showed the most potent protective effect and possesses an apparent role in protection against the development of intestinal inflammation.

Keywords: Intestinal injury; bromelain; indomethacin; papain; sulfasalazine.

Figure 1

Control rat group, (a): Photomicrograph of a section of higher magnification of a finger-like projection of the corium of the jejunum and the covering intestinal epithelium. Villi are covered with a simple columnar epithelium composed of absorptive enterocytes (red↑) and goblet cells (black↑). The core of the villous is formed of lamina propria (LP) that contains central lacteals (yellow ↑)

Figure 2

Positive Control Indo group, Higher magnification of the previous section of the of the jejunum nearby the ulcer showing diffuse inflammatory cell infiltrates (*) in the core of the villous with flattened epithelium and villous (v) blunting with multiple vacuolated areas (*). Notice absent goblet cells only columnar epithelium with pyknotic nuclei (↑) dilated congested blood vessels (BV) in the submucosa

Figure 3

Indomethacin + Bromelain rat group, Photomicrograph of a section in the jejunum of a male albino rat of bromelain treated group (group III), showing healthy normal intestinal, also there is a regularly arranged closely packed villi (v) lined by surface columnar cells with basal oval nuclei (black ↑) and goblet cells (red ↑). Notice many mitotic figures (Dot ↑)

Figure 4

Indomethacin + Papain rat group, Photomicrograph of a section in the jejunum showing regularly arranged closely packed villi lined by surface columnar cells with basal oval nuclei (red↑). Notice intraepithelial neutrophils (Dot ↑) are also seen and many mitotic figures (black ↑)

Figure 5

Indomethacin + Sulfasalazine rat group, (a): photomicrograph of a section in the jejunum of a male albino rat showing regularly arranged closely packed villi lined by surface columnar cells (black ↑) with basal oval nuclei and numerous goblet cells (red↑). Villi and few goblet cells (↑) H&E (×40)