Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

doi:10.3748/wjg.v20.i29.10158

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Randomized Controlled Trial

World J Gastroenterol. Aug 7, 2014; 20(29): 10158-10165
Published online Aug 7, 2014. doi: 10.3748/wjg.v20.i29.10158

Table 1 Histopathological damage scores for the control and the methotrexate-exposed groups, with and without antioxidant treatments

	Control	Model	MTX + NAC	MTX + AMF	MTX + ASC
Score	1 (0-3)	7 (6-9)^a	4 (3-6)^b	4.5 (3-5)^a	6 (5-6)^a^c^d

Data are expressed median (range).

^aP = 0.001 vs control group;

^bP = 0.001 vs control and model groups;

^cP < 0.05 vs MTX + NAC group;

^dP < 0.005 vs model and MTX + AMF groups. MTX: Methotrexate; NAC: N-acetyl cysteine; AMF: Amifostine.

Table 2 Effects of methotrexate and antioxidant treatments on body weight

	Control	Model	MTX + NAC	MTX + AMF	MTX + ASC
BW	387 (301-332)	318 (246-292.5)^a	295 (226-272)^b	306 (183-282.5)^a	340 (249-274)^c

Data are expressed median (range).

^aP < 0.005 vs control group;

^bP = 0.001 vs control group;

^cP < 0.01 vs control group. MTX: Methotrexate; NAC: N-acetyl cysteine; AMF: Amifostine; BW: Body weight; ASC: Ascorbic acid.

Table 3 Effects of methotrexate and antioxidant treatments on biochemical parameters of liver damage in liver tissues

Groups	MDA(nmol/g)	GSH(μmol/g)	SOD(U/g)	CAT(K/g)
Control	409 (352-466)	3.02 (2.85-3.43)	71.78 (61.88-97.81)	25.12 (21.08-29.28)
Model	455.5 (419-516)^a	2.52 (2.07-3.34)^a	61.46 (58.27-67.75)^a	23.89 (20.89-30.75)
MTX + NAC	436 (369-476)	3.22 (2.54-3.62)^b	69.22 (61.13-100.88)^c	22.16 (19.45-22.48)
MTX + AMF	442.5 (323-490)	2.92 (2.21-3.53)	63.78 (40.82-124.27)	20.88 (17.27-21.78)^d
MTX + ASC	420.5 (355-463)	2.84 (2.33-3.48)	61.81 (46.76-85.71)	21.51 (20.63-22.78)

Data are expressed median (range).

^aP < 0.05 vs control group;

^bP < 0.05 vs model group;

^cP < 0.01 vs model group;

^dP < 0.05 vs control vs model groups. MTX: Methotrexate; NAC: N-acetyl cysteine; AMF: Amifostine; ASC: Ascorbic acid; MDA: Malondialdehyde; GSH; Glutathione; SOD: Superoxide dismutase; CAT: Catalase.

Table 4 Effects of methotrexate and antioxidant treatments on oxidant-antioxidant parameters in serum

Groups	TAC(mmol/L)	TOS(mmol/L)	XO(U/g)
Control	1.3 (1.1-1.38)	13.05 (9.3-27.3)	2.41 (1.80-14.60)
Model	1.2 (0.9-1.5)	25.4 (16.1-49.7)^a	1.27 (0.56-17.35)^a
MTX + NAC	1.27 (1.15-1.4)	26.7 (18.5-62.2)^b	1.41 (0.68-2.75)^a
MTX + AMF	1.22 (0.3-1.4)	27.2 (10-61.2)	1.60 (0.41-2.29)^c
MTX + ASC	1.31 (0.95-1.44)	26.85 (12.2-97)^a	1.10 (0.24-1.48)^c^d

Data are expressed median (min-max).

^aP < 0.05 vs control group;

^bP = 0.005 vs control group;

^cP < 0.01 vs control group;

^dP < 0.05 vs MTX + AMF group. TAC: Total antioxidant capacity; TOS: Total oxidant status; XO: Xanthine oxidase; MTX: Methotrexate; AMF: Amifostine; NAC: N-acetyl cysteine; ASC: ascorbic acid.

Table 5 Effects of methotrexate and antioxidant treatments on biochemical parameters of liver damage in serum

Groups	ALT(U/L)	AST(U/L)	ALP(U/L)	T. bilirubin(mg/dL)
Control	36 (34-48)	93.5 (74-135)	197 (168-271)	0.1 (0.1-0.2)
Model	119.5 (62-141)^a	49 (33-73)^a	102 (76-437)	0.1 (0.1-0.2)
MTX + NAC	107.5 (66-161)^b	50 (35-80)^b	84.5 (72-123)^a	0.1 (0.1-0.2)
MTX + AMF	74.5 (28-219)	31 (11-49)^a^c	57.5 (25-138)^a^e	0.1 (0.1-0.8)
MTX + ASC	91.5 (56-141)^b	45 (32-58)^a^d	87 (64-108)^a	0.15 (0.1-0.2)

Data are expressed median (range).

^aP = 0.001 vs control group;

^bP < 0.005 vs control group;

^cP < 0.05 vs model and MTX+NAC groups;

^dP < 0.05 vs MTX + AMF group;

^eP < 0.05 vs Model group. MTX: Methotrexate; NAC: N-acetyl cysteine; AMF: Amifostine; ASC: Ascorbic acid; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; T. bilirubin: Total bilirubin.

Citation: Akbulut S, Elbe H, Eris C, Dogan Z, Toprak G, Otan E, Erdemli E, Turkoz Y. Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats. World J Gastroenterol 2014; 20(29): 10158-10165
URL: https://www.wjgnet.com/1007-9327/full/v20/i29/10158.htm
DOI: https://dx.doi.org/10.3748/wjg.v20.i29.10158