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. 2024 Jun 30;13(7):486.
doi: 10.3390/biology13070486.

Dietary Chitosan Attenuates High-Fat Diet-Induced Oxidative Stress, Apoptosis, and Inflammation in Nile Tilapia (Oreochromis niloticus) through Regulation of Nrf2/Kaep1 and Bcl-2/Bax Pathways

Aya G Rashwan  1 , Doaa H Assar  2 , Abdallah S Salah  3   4 , Xiaolu Liu  5   6 , Ibrahim I Al-Hawary  1 , Mohammed H Abu-Alghayth  7 , Shimaa M R Salem  8 , Karim Khalil  9 , Nemany A N Hanafy  10 , Alaa Abdelatty  11 , Luyang Sun  5   6 , Zizy I Elbialy  1
Affiliations

Dietary Chitosan Attenuates High-Fat Diet-Induced Oxidative Stress, Apoptosis, and Inflammation in Nile Tilapia (Oreochromis niloticus) through Regulation of Nrf2/Kaep1 and Bcl-2/Bax Pathways

Aya G Rashwan et al. Biology (Basel). .

Abstract

Fatty liver injury is a prevalent condition in most farmed fish, yet the molecular mechanisms underpinning this pathology remain largely elusive. A comprehensive feeding trial spanning eight weeks was conducted to discern the potential of dietary chitosan in mitigating the deleterious effects of a high-fat diet (HFD) while concurrently exploring the underlying mechanism. Growth performance, haemato-biochemical capacity, antioxidant capacity, apoptotic/anti-apoptotic gene expression, inflammatory gene expression, and histopathological changes in the liver, kidney, and intestine were meticulously assessed in Nile tilapia. Six experimental diets were formulated with varying concentrations of chitosan. The first three groups were administered a diet comprising 6% fat with chitosan concentrations of 0%, 5%, and 10% and were designated as F6Ch0, F6Ch5, and F6Ch10, respectively. Conversely, the fourth, fifth, and sixth groups were fed a diet containing 12% fat with chitosan concentrations of 0%, 5%, and 10%, respectively, for 60 days and were termed F12Ch0, F12Ch5, and F12Ch10. The results showed that fish fed an HFD demonstrated enhanced growth rates and a significant accumulation of fat in the perivisceral tissue, accompanied by markedly elevated serum hepatic injury biomarkers and serum lipid levels, along with upregulation of pro-apoptotic and inflammatory markers. In stark contrast, the expression levels of nrf2, sod, gpx, and bcl-2 were notably decreased when compared with the control normal fat group. These observations were accompanied by marked diffuse hepatic steatosis, diffuse tubular damage, and shortened intestinal villi. Intriguingly, chitosan supplementation effectively mitigated the aforementioned findings and alleviated intestinal injury by upregulating the expression of tight junction-related genes. It could be concluded that dietary chitosan alleviates the adverse impacts of an HFD on the liver, kidney, and intestine by modulating the impaired antioxidant defense system, inflammation, and apoptosis through the variation in nrf2 and cox2 signaling pathways.

Keywords: apoptosis; bcl-2/bax; chitosan; high-fat diet; nrf2/kaep1; oxidative stress.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Representative photomicrographs of kidneys from different treatment groups. (A) F6Ch0 shows normal tubular and glomerular structure with moderately vacuolar cytoplasm in addition to adequate interstitial cells. (B) F6Ch5 shows nearly normal histological structure with less vacuolated cytoplasm in addition to slight interstitial cell infiltration (thin arrow). (C) F6Ch10 shows focal tubular degeneration (thin arrow) with interstitial inflammatory aggregations (thick arrow). (D) F12Ch0 shows diffuse tubular damage represented by severe necrotic tubular epithelial cells (thin arrows), intraluminal esinophilic cellular cast (star), and interstitial fibrosis (thick arrow) admixed with lymphocytes and numerous RBCs (arrowhead). (E) F12Ch5 shows mild tubular necrosis (thin arrows). (F) F12Ch10 shows mostly normal tubular endothelial lining with less vacuolation (thin arrows) and little interstitial inflammatory cell infiltration (thick arrow). Scale bar = 50 μm.
Figure 2
Figure 2
Representative photomicrographs of intestines from different treatment groups. (A) F6Ch0 shows a normal structure of intestinal villi with an intact mucous membrane. (B) F6Ch5 shows normal intestinal mucosa except for a few intestinal vacuoles (thin arrow). (C) F6Ch10 shows mild intestinal vacuolation (thin arrows). (D) F12Ch0 shows shortened intestinal villi with many vacuoles (thin arrow). (E) F123Ch5 shows minimal apical loss (thick arrow) and expanded intestinal mucosa. (F) F12Ch10 shows elongation of the intestinal villi, slight apical mucosal loss (thick arrow), and little intestinal vacuolation (thin arrow). Scale bar = 50 μm.
Figure 3
Figure 3
Representative photomicrographs of livers from different treatment groups. (A) F6Ch0 shows normal hepatic architecture with a normal vacuolation appearance. (B) F6Ch5 shows mostly normal hepatocytes and normal lipid vacuoles (thin arrow) with a few slight degenerative changes (thick arrow). (C) F6Ch10 shows hydropic degeneration (thin arrow) with slight blood vessel dilatation. (D) F12Ch0 shows marked hepatocellular necrosis with a loss of most nuclei (thin arrow). (E) F12Ch5 shows relatively vacuolated cytoplasm with intact nuclei. (F) F12Ch10 shows normal hepatocytes with slight degenerative changes in some cells (thick arrow). Scale bar = 50 μm.
Figure 4
Figure 4
Liver histological morphology in Nile tilapia fed with different experimental diets for 8 weeks. Liver tissue sections were stained with Masson trichrome stain. (A): F6Ch0; (B): F12Ch0 (accumulation of collagen fibers (CFs)); (C): F6Ch5; (D): F6Ch10; (E): F12Ch5 (mild accumulation of collagen fibers (CFs)); (F): F12Ch10. Scale bar = 200 μm.
Figure 5
Figure 5
Histological liver sections of Nile tilapia fed with different experimental diets for 8 weeks. Tissue sections were stained with a periodic acid Schiff reagent (PAS) stain. (A): F6Ch0 (accumulated glycogen (AG)); (B): F12Ch0 (slight glycogen (SG)); (C): F6Ch5 (mild glycogen (MG)); (D): F6Ch10 (accumulated glycogen (AG)); (E): F12Ch5 (slight glycogen (SG)); (F): F12Ch10 (mild glycogen (MG)). Scale bar = 200 μm.
Figure 6
Figure 6
Differential expression of different antioxidant genes in the liver and intestine of Nile tilapia groups fed on normal and high-fat diets with chitosan. (A,B) Nrf2: Nuclear factor erythroid 2-related factor 2, (C,D) Kaep1: Kelch-like ECH-associated protein 1, (E,F) GPx: Glutathione peroxidase, (G,H) SOD: Superoxide dismutase. Columns with different superscript letters in the same figure are significantly different (p ≤ 0.05).
Figure 7
Figure 7
Differential expression of apoptosis-related genes in the liver and tight junction-related genes in the intestine of Nile tilapia groups fed on normal and high-fat diets with chitosan. (A) Bax: Bcl-2 associated X-protein, (B) Bcl2: B-cell lymphoma 2, (C) Cyc1: Cytochrome c, (D) Casp3: Cysteine-aspartic acid protease3 in the liver, (E) Casp9: Cysteine-aspartic acid protease9, (F) cldn7: Claudin7, (G) cldn3c: Claudin3c, (H) tjp1: Zonula occludens-1, (I) tjp2: Zonula occludens-2, (J) casp3: Cysteine-aspartic acid protease3 in the intestine. Columns with different superscript letters in the same figure are significantly different (p ≤ 0.05).
Figure 8
Figure 8
Differential expression of immune-related genes in the liver and intestine of Nile tilapia groups fed on normal and high-fat diets with chitosan. (A,B) cox2: Cyclooxygenase 2 in the liver and intestine, (C,D) tnf-a: Tumor necrosis factor alpha, (E,F) il-1β: Interleukin-1beta, (G,H) il-10: Interleukin-10. Columns with different superscript letters in the same figure are significantly different (p ≤ 0.05).
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Grants and funding

This work was funded by the Deanship of Graduate Studies and Scientific Research at the University of Bisha, Saudi Arabia, through the Promising Program under grant number (UB-Promising-34-1445).

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