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, 2018, 4039753
eCollection

Antifibrogenic Influence of Mentha piperita L. Essential Oil Against CCl 4-Induced Liver Fibrosis in Rats

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Antifibrogenic Influence of Mentha piperita L. Essential Oil Against CCl 4-Induced Liver Fibrosis in Rats

Hanan A Ogaly et al. Oxid Med Cell Longev.

Abstract

Essential oils of some aromatic plants provide an effective nonmedicinal option to control liver fibrosis. Mentha piperita L. essential oil (MPEO) have been reported to possess protective effects against hepatotoxicity. However, its effect against liver fibrosis remains unknown. The present study investigated the antifibrogenic potential of MPEO and its underlying mechanisms. Forty male rats divided into 4 groups were used: group 1 served as normal control, group 2 (liver fibrosis) received CCl4 (2.5 mL/kg, IP, twice weekly) for 8 weeks, group 3 concurrently received CCl4 plus MPEO (50 mg/kg, IP, daily, from the 3rd week), and group 4 received MPEO only. MPOE significantly improved the liver injury markers, lipid peroxidation (LPO), antioxidant capacity, CYP2E1 gene expressionand liver histology. Furthermore, MPOE ameliorated liver fibrosis as evidenced by the reduced expression of desmin, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and SMAD3 proteins. In addition, MPOE counteracted the p53 upregulation induced by CCl4 at both mRNA and protein levels. In conclusion, MPOE could effectively attenuate hepatic fibrosis mainly through improving the redox status, suppressing p53 and subsequently modulating TGF-β1 and SMAD3 protein expression. These data promote the use of MPOE as a promising approach in antifibrotic therapy.

Figures

Figure 1
Figure 1
Antioxidant volatile constituents found in Mentha piperita essential oil.
Figure 2
Figure 2
Histopathological examination of the liver tissues (H&E, ×200). (a) Group 1 (normal control) showing normal histological picture of the liver. (b) Group 2 (fibrosis control) showing fatty degeneration of the hepatocytes, hepatocellular necrosis, and mononuclear inflammatory cells aggregation along the collagenous septa. (c) Group 3 (MPEO-treated) showing moderate hepatocellular necrosis, marked reduction of collagenous septa formation and mononuclear inflammatory cells aggregation. (d) Group 4 (MPEO control) showing normal hepatic cellular architecture.
Figure 3
Figure 3
Photomicrograph of liver stained with MT stain (×100). (a and d) The normal control (group 1) and MPEO control (group 4) showing normal distribution of collagen fibers in the portal areas. (b) Group 2 (fibrosis control) showing marked fibrous bridging with excessive collagen fibers deposition. (c) Group 3 (MPEO-treated) showing marked attenuation of collagen fibers distribution and deposition. (e) Bar chart represents the hepatic fibrosis expressed as fibrosis %. Mean values with different superscripts are significantly different (p < 0.05).
Figure 4
Figure 4
Representative α-SMA immunohistochemistry in liver tissues of the different experimental groups (×200). (a and d) The normal control (group 1) and MPEO control (group 4) showing α-SMA staining in the smooth muscle cells of the hepatic vessels. (b) Liver fibrosis control (group 2) showing strong immunostaining reaction in myofibroblast cells. (c) MPEO-treated (group 3) showing marked reduction in immunopositive reactive areas. (e) Bar chart represents the α-SMA immunohistochemistry expressed as area %. Mean values with different superscripts are significantly different (p < 0.05).
Figure 5
Figure 5
Representative desmin immunohistochemistry in liver tissues of the different experimental groups (×200). (a and d) The normal control (group 1) and MPEO control (group 4) showing very weak immunopositive reaction. (b) Liver fibrosis control (group 2) showing strong immunostaining reaction in perisinusoidal cells. (c) MPEO-treated (group 3) showing weak immunostaining of perisinusoidal cells. (e) Bar chart represents desmin immunohistochemistry expressed as area %. Mean values with different superscripts are significantly different (p < 0.05).
Figure 6
Figure 6
Representive TGF-β1 immunohistochemistry in liver tissue of the different experimental groups (×200). (a and d) The normal control (group 1) and MPEO control (group 4) showing weak immunopositive reaction in portal areas. (b) Liver fibrosis control (group 2) showing intense immunostaining in periductal cells in the portal tract, in perisinusoidal cells, around the blood vessels, and in sinusoidal lining cells. (c) MPEO-treated (group 3) showing mild reaction in some perisinusoidal cells. (e) Bar chart represents the TGF-β1 immunohistochemistry in liver expressed as area %. Mean values with different superscripts are significantly different (p < 0.05).
Figure 7
Figure 7
Representive SMAD3 immunohistochemistry in liver tissues of the different experimental groups. (a and e) The normal control and MPEO control (×200). (b) Liver fibrosis control (group 2) showing intense immunostaining reaction (×100). (c) Liver fibrosis control (group 2) showing strong cytoplasmic and nuclear staining (×200). (d) MPEO-treated (group 3) showing marked reduction of immunostaining reaction (×200). (f) Bar chart represents SMAD3 immunohistochemistry expressed as area %. Mean values with different superscripts are significantly different (p < 0.05).
Figure 8
Figure 8
Quantitative real-time PCR of Tp53 and CYP2E1 mRNA in liver tissues of the different experimental groups. Values are expressed as means ± SD. GAPDH was used as an invariant housekeeping control gene for calculating the fold changes (RQ) in mRNA levels. Mean values having different letters are significantly different (p < 0.05).
Figure 9
Figure 9
Representive p53 immunohistochemistry in liver tissues of the different experimental groups (×400). (a and d) The normal control and MPEO control very weak immunopositive reaction. (b) Liver fibrosis control (group 2) showing intense immunostaining in most of the hepatic cells. (c) MPEO-treated (group 3) showing immunopositive reaction in some hepatic cells. (e) Bar chart represents the p53 immunohistochemistry in liver tissues expressed as area %. Mean values with different superscripts are significantly different (p < 0.05).

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