The beneficial effects of Montelukast against 2,3,7,8-tetrachlorodibenzo- p -dioxin toxicity in female reproductive system in rats

To determine the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive system and the beneficial effects of Montelukast (ML) with histological and biochemical analysis.

METHODS:

Rats were randomly divided into four equal groups (control, TCDD, ML and TCDD+ML). Tissue samples were collected on day 60 and oxidative status and histological alterations were analyzed.

RESULTS:

The results showed a significant increase in oxidative and histological damage on uterine and ovarian tissues. Otherwise, the oxidative and histological damages caused by TCDD were prevented with ML treatment.

CONCLUSION:

The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on female reproductive system were reversed with Montelukast treatment. Therefore, we claimed that ML treatment might be useful for TCDD toxicity.

Key words:
Tetrachlorodibenzodioxin; Oxidative Stress; Leukotriene Antagonists; Ovary; Uterus.

Authorship

Rauf Melekoglu

Assistant Professor, Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Inonu, Malatya, Turkey. Acquisition of data, manuscript writing.University of InonuTurkeyMalatya, TurkeyAssistant Professor, Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Inonu, Malatya, Turkey. Acquisition of data, manuscript writing.

Osman Ciftci

Associate Professor, Department of Medical Pharmacology, Faculty of Medicine, University of Inonu, Malatya, Turkey. Design of the study, manuscript writing.University of InonuTurkeyMalatya, TurkeyAssociate Professor, Department of Medical Pharmacology, Faculty of Medicine, University of Inonu, Malatya, Turkey. Design of the study, manuscript writing.

Aslı Cetin

Assistant Professor, Department of Histology, Faculty of Medicine, University of Inonu, Malatya, Turkey. Histological examinations.University of InonuTurkeyMalatya, TurkeyAssistant Professor, Department of Histology, Faculty of Medicine, University of Inonu, Malatya, Turkey. Histological examinations.

Nese Basak

PhD, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, University of Inonu, Malatya, Turkey. Biochemical examinations.University of InonuTurkeyMalatya, TurkeyPhD, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, University of Inonu, Malatya, Turkey. Biochemical examinations.

Ebru Celik

Associate Professor, Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Inonu, Malatya, Turkey. Design of the study.University of InonuTurkeyMalatya, TurkeyAssociate Professor, Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Inonu, Malatya, Turkey. Design of the study.

Correspondence: Dr. Osman Ciftci Department of Pharmacology, University of Inonu 44 280 Malatya, Turkey Phone: +905325646122 Fax: +90422 3411216 osmciftci@gmail.com

Conflict of interest: none

SCIMAGO INSTITUTIONS RANKINGS

Figures | Tables

Figures (5)
Tables (2)

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FİGURE 1
Ovaries from control rats showing normal histological appearance. Different follicles types (A,B,C) and corpus luteum (white star) (A) were observed in ovary. Multilaminary (black arrow) (A) Secondary (white arrows) (B,C) follicles were observed in control group. (A: H-E; x10, B, C: H-E; x20)

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FİGURE 2
In TCDD group, we detected significantly higher scores for follicular degeneration (white arrows) (A,C,E), vascular congestion (white stars) (A,C), edema, hemorrhage (black arrows) (A,C,F) and mononuclear cell infiltration (A-F). (A: H-E; x10, B,C,D,E,F: H-E; x20)

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FİGURE 3
In TCDD + ML group showed a significant level of improvement in ovarian follicle morphology, edema, mononuclear cell infiltration, vascular congestion (white star) (B) and hyperemia as compared with the TCDD group. Multilaminary primary follicles (white arrow) (C) and improved corpus luteum (black arrows) (A,B) were observed in this group. (A: H-E; x10, B: H-E; x20, C: H-E; x40)

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FİGURE 4
Normal histological appearance were observed in ML group. Secondary follicles (white arrows) (A), unilaminary primary follicle (black arrow) (B) and graffian follicles (white star) (C) were observed in ML group. (A: H-E; x10, B: H-E; x40, C: H-E; x20)

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FİGURE 5
Normal endometrial epithelium (white arrows) in control (A) and ML (D) groups, thin endometrial epithelium (black arrows) in TCDD group (B). We observed improvement in epithelial appearance (thin black arrows) in TCDD + ML group (C). (A-D: H-E; x20)

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TABLE 1
The levels of SOD, CAT, GSH and TBARS in rat uterus tissue. ±SD.

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TABLE 2
The levels of SOD, CAT, GSH and TBARS in rat ovarium tissue. ±SD.

FİGURE 1 Ovaries from control rats showing normal histological appearance. Different follicles types (A,B,C) and corpus luteum (white star) (A) were observed in ovary. Multilaminary (black arrow) (A) Secondary (white arrows) (B,C) follicles were observed in control group. (A: H-E; x10, B, C: H-E; x20)

FİGURE 2 In TCDD group, we detected significantly higher scores for follicular degeneration (white arrows) (A,C,E), vascular congestion (white stars) (A,C), edema, hemorrhage (black arrows) (A,C,F) and mononuclear cell infiltration (A-F). (A: H-E; x10, B,C,D,E,F: H-E; x20)

FİGURE 3 In TCDD + ML group showed a significant level of improvement in ovarian follicle morphology, edema, mononuclear cell infiltration, vascular congestion (white star) (B) and hyperemia as compared with the TCDD group. Multilaminary primary follicles (white arrow) (C) and improved corpus luteum (black arrows) (A,B) were observed in this group. (A: H-E; x10, B: H-E; x20, C: H-E; x40)

FİGURE 4 Normal histological appearance were observed in ML group. Secondary follicles (white arrows) (A), unilaminary primary follicle (black arrow) (B) and graffian follicles (white star) (C) were observed in ML group. (A: H-E; x10, B: H-E; x40, C: H-E; x20)

FİGURE 5 Normal endometrial epithelium (white arrows) in control (A) and ML (D) groups, thin endometrial epithelium (black arrows) in TCDD group (B). We observed improvement in epithelial appearance (thin black arrows) in TCDD + ML group (C). (A-D: H-E; x20)

TABLE 1 The levels of SOD, CAT, GSH and TBARS in rat uterus tissue. ±SD.

	TBARS (nmol/g tissue)	Reduced GSH nmol/ml	CAT kU/mg protein	SOD (U/mg protein)
Control	5.18±1.12^a	151.7±18.1^a	1.23±0.09^a	18.12±3.17^a
TCDD	8.93±1.21^b	104.8±11.2^b	0.96±0.05^b	10.01±1.14^b
ML	5.75±1.35^a	162.5±16.8^a	1.25±0.08^a	16.52±1.82^a
TCDD+ ML	6.51±0.97^c	131.6±21.1^c	1.03±0.09^b	13.15±2.23^a

SOD; superoxide dismutase; CAT: catalase; GSH: glutathione, TBARS: thiobarbituric acid reactive substance; ML: montelukast; TCDD: 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Means bearing different superscripts within same column were significantly different (p<0.01).

TABLE 2 The levels of SOD, CAT, GSH and TBARS in rat ovarium tissue. ±SD.

	TBARS (nmol/g tissue)	Reduced GSH nmol/ml	CAT kU/mg protein	SOD (U/mg protein)
Control	6.13±0.92^a	186.1±23.7^a	0.96±0.10^a	22.06±4.51^a
TCDD	10.05±1.75^b	121.4±21.4^b	0.66±0.08^b	14.18±3.41^b
ML	6.88±1.42^a	171.8±27.5^a	1.01±0.09^a	24.10±5.21^a
TCDD +ML	7.28±1.22^a	158.4±19.5^ac	0.84±0.09^c	21.85±3.12^a

ML: montelukast; TCDD: 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Means bearing different superscripts within same column were significantly different (p<0.01).

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