Hepatotoxicity Induced by Arsenic Trioxide in Adult Mice and Their Progeny
In this investigation, we have evaluated the effects of
arsenic trioxide on hepatic function in pregnant and lactating Swiss
albino mice and their suckling pups. Experiments were carried out on
female mice given 175 ppm As2O3 in their drinking water from the
14th day of pregnancy until day 14 after delivery. Our results showed
a significant decrease in plasma levels of total protein and albumin,
cholesterol and triglyceride in As2O3 treated mice and their pups. The
hyperbilirubinemia and the increased plasma total alkaline
phosphatase activity suggested the presence of cholestasis.
Transaminase activities as well as lactate deshydrogenase activity in
plasma, known as biomarkers of hepatocellular injury, were elevated
indicating hepatic cells’ damage after treatment with As2O3.
Exposure to arsenic led to an increase of liver thiobarbituric acid
reactive substances level along with a concomitant decrease in the
activities of superoxide dismutase, catalase and glutathione
peroxidase and in glutathione.
[1] R. Gupta, G.M. Kannan, M. Sharma, and S.J.S. Flora, “Therapeutic
effects of Moringa oleifera on arsenic-induced toxicity in rats.”
Environmental Toxicology and Pharmacology, vol. 20, pp. 456-464,
2005.
[2] Y. Jin, G. Sun, X. Li, G. Li, C. Lu, and L. Qu, “Study on the toxic
effects induced by different arsenicals in primary cultured rat astroglia.”
Toxicology and Applied Pharmacology, vol. 196, pp. 396–403, 2004.
[3] C.H. Tseng, C.K. Chong, C.J. Chen, and T.Y. Tai, “Dose-response
relationship between peripheral vascular disease and ingested inorganic
arsenic among residents in Blackfoot disease endemic villages in
Taiwan.” Atherosclerosis, vol. 120, pp. 125–133, 1996.
[4] C.J. Chen, Y.M. Hsueh, M.S. Lai, M.P. Shyu, S.Y. Chen, M.M. Wu,
T.L. Kuo, and T.Y. Tai, “Increased prevalence of hypertension and long
term arsenic exposure.” Hypertension, vol. 25, pp. 53–60, 1995.
[5] P.P. Simeonova, and M.I. Luster, “Arsenic and atherosclerosis.”
Toxicology and Applied Pharmacology, vol. 198, pp. 444–449, 2004.
[6] R. Iffland, D. Seiler, G. Hans, A. Siegel, and H. Siegal, “Handbook on
metals in clinical and analytical chemistry.” New York: Marcel Dekkar,
Inc, 1994, pp. 237–253.
[7] Z. Li, F. Piao, S. Liu, Y. Wang, and S. Qu, “Subchronic exposure to
arsenic trioxideinduced oxidative DNA damage in kidney tissue of
mice.” Experimental and Toxicologic Pathology, vol. 62, pp. 543–547,
2010.
[8] G.K. Harris, and X. Shi, “Signalling by carcinogenic metals and metalinduced
reactive oxygen species.” Mutation Research, vol. 533, pp. 183–
200, 2003.
[9] G. Concha, G. Vogler, D. Lezcano, B. Nermell, and M. Vahter,
“Exposure to inorganic arsenic metabolites during early human
development.” Toxicology Sciences, vol. 44, pp. 185–90, 1998.
[10] V. Devesa, B.M. Adair, J. Liu, M.P. Waalkes, B.A. Diwan, M. Styblo,
and D.J. Thomas, “Arsenicals in maternal and foetal mouse tissues after
gestational exposure to arsenite.” Toxicology, vol. 224, pp. 147–55,
2006.
[11] V.H. Ferm, and S.J. Carpenter, “Malformations induced by sodium
arsenate.” Journal of Reproduction and Fertility, vol. 17, pp. 199-201,
1967.
[12] R.D. Hood, “Effects of sodium arsenite on foetal development.”
Environmental Contamination and Toxicology, vol. 7, pp. 216-222,
1972.
[13] A.R. Beaudoin, “Teratogenicity of sodium arsenate in rats.” Teratology,
vol. 10, pp. 153-158, 1974.
[14] M.P. Waalkes, J.M. Ward, J. Liu, and B.A. Diwan, “Transplacental
carcinogenicity of inorganic arsenic in the drinking water: induction of
hepatic, ovarian, pulmonary, and adrenal tumors in mice.” Toxicol Appl
Pharmacol, vol. 186, pp. 7–17, 2003.
[15] M.P. Waalkes, J. Liu, J.M. Ward, D.A. Powell, and B.A. Diwan,
“Urogenital carcinogenesis in female CD1 mice induced by in utero
arsenic exposure is exacerbated by postnatal diethylstilbestrol
treatment.” Cancer Research, vol. 66, pp. 1337–1345, 2006.
[16] A.H. Smith, G. Marshall, Y. Yuan, C. Ferreccio, J. Liaw, E.O. von, C.
Steinmaus, M.N. Bates, and S. Selvin, “Increased mortality from lung
cancer and bronchiectasis in young adults after exposure to arsenic in
utero and in early childhood.” Environmental Health Perspectives, vol.
114, pp. 1293–1296, 2006.
[17] G. Tournel, V. Gnemmi, and V. Hédouin, “Acute arsenic poisoning:
clinical, toxicological, histopathological, and forensic features.” Journal
of Forensic Sciences, vol. 56, pp. 275–279, 2011.
[18] J.W.E. Harrison, E.W. Packman, and D.D. Abbott, “Acute oral toxicity
and chemical and physical properties of arsenic trioxides.” American
Medical Association Archives of Industrial Health, vol. 17, pp. 118-123,
1958.
[19] K.L. Fishbeck, and K.M. Rasmussen, “Effects of repeated cycles on
maternal nutritional status, lactational performance and litter growth in
ad libitum-fed and chronically food-restricted rats.” The Journal of
Nutrition, vol. 117, pp. 1967–1975, 1987.
[20] H.H. Draper, and M. Hadley, “Malondialdehyde determination as index
of lipid peroxidation.” Methods in Enzymology, vol. 86, pp. 421-431,
1990.
[21] C. Beauchamp, and I. Fridovich, “Superoxide dismutase: improved
assays and an assay applicable to acrylamide gel.” Analytical
Biochemistry, vol. 44, pp. 276–287, 1971.
[22] H. Aebi, “Catalase in vitro.” Methods in Enzymology, vol. 105, pp. 121-
126, 1984.
[23] L. Flohe, and W.A. Gunzler, “Assays of glutathione peroxidase.”
Method Enzymol, vol. 105, pp. 114-121, 1984.
[24] G.L. Ellman, “Tissue sulfhydryl groups.” Archives of Biochemistry and
Biophysics, vol. 82, pp. 70-77, 1959.
[25] D.J. Jollow, J.R. Mitchell, N. Zampaglione, and J.R. Gillette,
“Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic
metabolite.” Pharmacology, vol. 11, pp. 151-169, 1974.
[26] C. Watanabe, T. Inaoka, T. Mastui, K. Ishigaki, N. Murayama, and R.
Ohtsuka. Effects of arsenic on younger generations. Journal of
Environmental Science and Health, vol. 38, pp. 129-139, 2003.
[27] D.N. Guha Mazumder, “Effect of chronic intake of arsenic contaminated
water on liver.” Toxicology and Applied Pharmacology, vol. 206, pp.
169–175, 2005.
[28] M. Messarah, F. Klibet, A. Boumendjel, C. Abdennour, N. Bouzerna,
M.S. Boulakoud, and A. El Feki, “Hepatoprotective role and antioxidant
capacity of selenium on arsenic-induced liver injury in rats.”
Experimental and Toxicologic Pathology, vol. 64(3):pp. 167-74, 2012.
[29] N.J. Chinoy, and M.R. Memon, “Beneficial effects of some vitamins and
calcium on fluoride and aluminium toxicity on gastrocnemius muscle
and liver of male mice.” Fluoride, vol. 34, pp. 21–33, 2001.
[30] S. Pal, and A.K. Chatterjee, Protective effect of N-acetylcysteine against
arsenic-induced depletion in vivo of carbohydrate.” Drug and Chemical
Toxicology, vol. 27, pp. 179–189, 2004.
[31] S. Pal, and A.K. Chatterjee, “Prospective protective role of melatonine
against arsenic-induced metabolic toxicity in Wistar rats.” Toxicology,
vol. 208, pp. 25-33, 2005.
[32] Y. Hu, L. Su, and E.T. Snow, “Arsenic toxicity is enzyme specific and
its effects on ligation are not caused by the direct inhibition of DNA
repair enzymes.” Mutation Research, vol. 408, pp. 203–218, 1998.
[33] E. Lenartowicz, “A complex effect of arsenite on the formation of alphaketoglutarate
in rat liver mitochondria.” Archives of Biochemistry and
Biophysics, vol. 283, pp. 388–396, 1990.
[34] A.K. Patlolla, C. Barnes, C. Yedjou, V.R. Velma, and P.B. Tchounwou,
“Oxidative stress, DNA damage, and antioxidant enzyme activity
induced by hexavalent chromium in sprague-dawley rats.”
Environmental Toxicology, vol. 24, pp. 66-73, 2009.
[35] F.M. El-Demerdash, M.I. Yousef, and F.A. Elaswad, “Biochemical
study on the protective role of folic acid in rabbits treated with
chromium (VI).” Journal of Environmental Science and Health, Part B,
vol. 41, pp. 731–746, 2006.
[36] C.L. Gaskill, L.M. Miller, J.S. Mattoon, W.E. Hoffmann, S.A. Burton,
H.C.J. Gelens, S.L. Ihle, J.B. Miller, D.H. Shaw, and A.E. Cribb, “Liver
histopathology and liver serum alanine aminotransferase and alkaline
phosphatase activities in epileptic dogs receiving Phenobarbital.”
Veterinary Pathology, vol. 42, pp. 147-160, 2005.
[37] A. Albores, M.E. Cebria´n, P.H. Bach, J.C. Connelly, R.H. Hinton and
J.M. Bridges, “Sodium arsenite induced alterations in bilirubin excretion
and heme metabolism.” Journal of Biochemical Toxicology, vol. 4, pp.
73–78, 1989.
[38] A. Hernandez-Zavala, L.M. Del Razo, C. Aguilar, G.G. Garcia-Vargas,
V.H. Borja, and M.E. Cebrian, “Alteration in bilirubin excretion in
individuals chronically exposed to arsenic in Mexico.” Toxicology
Letters, vol. 99, pp. 79-84, 1998.
[39] S. Das, A. Santra, S. Lahiri, and D.N. Guha Mazumder, “Implications of
oxidative stress and hepatic cytokine (TNF-alpha and IL-6) response in
the pathogenesis of hepatic collagenesis in chronic arsenic toxicity.”
Toxicology and Applied Pharmacology, vol. 204, pp. 18–26, 2005.
[40] S.X. Liu, M. Athar, I. Lippai, C. Waldren, and T.K. Hei, “Induction of
oxyradicals by arsenic: implication for mechanism of genotoxicity.”
Proceedings of the National Academy of Sciences USA, vol. 98, pp.
1643–1648, 2001.
[41] K.T. Yamanaka, R. Sawamura, A. Hasegawa, and S. Okada, “Induction
of DNA damage by dimethyl arsine, a main metabolite of inorganic
arsenics, is for the major part due to its peroxyl radical.” Biochemical
and Biophysical Research Communications, vol. 168, pp. 58–64, 1989.
[42] N.J. Chinoy, and S.D. Shah, “Biochemical effects of sodium fluoride
and arsenic trioxide and their reversal in brain of mice.” Fluoride, vol.
37, pp. 80-87, 2004.
[43] S. Maiti, and A.K. Chatterjee, “Effects in levels of glutathione and some
related enzymes in tissues after an acute arsenic exposure in rats and
their relationship to dietary protein deficiency.” Archives of Toxicology,
vol. 75, pp. 531-537, 2001.
[44] S.J.S. Flora, “Arsenic-induced oxidative stress and its reversibility.”
Free Radical Biology and Medicine, vol. 51, pp. 257–281, 2011.
[45] G. Saxena, and S.J.S. Flora, “Lead induced oxidative stress and
haematological alterations and their response to combined
administration of calcium disodium EDTA with a thiol chelator in rats.”
Journal of Biochemical and Molecular Toxicology, vol. 18, pp. 221–
233, 2004.
[46] R. Gupta, G.M. Kannan, M. Sharma, and S.J.S. Flora, “Therapeutic
effects of Moringa oleifera on arsenic-induced toxicity in rats.”
Environmental Toxicology and Pharmacology, vol. 20, pp. 456-464,
2005.
[47] M.N. Kirkman, and G.F. Gaetani, “Catalase: a tetrameric enzyme with
four tightly bound molecules of NADPH. Proceedings of the National
Academy of Sciences USA, vol. 81, pp. 4343–4347, 1984.
[48] F. Nielson, “Other trace elements.” In: Ziegler, E.E., Filer, L.J. (Eds.),
Present Knowledge in Nutrition, seventh ed. Washington, DC: ILSI
Press, 1995, pp. 353–377.
[1] R. Gupta, G.M. Kannan, M. Sharma, and S.J.S. Flora, “Therapeutic
effects of Moringa oleifera on arsenic-induced toxicity in rats.”
Environmental Toxicology and Pharmacology, vol. 20, pp. 456-464,
2005.
[2] Y. Jin, G. Sun, X. Li, G. Li, C. Lu, and L. Qu, “Study on the toxic
effects induced by different arsenicals in primary cultured rat astroglia.”
Toxicology and Applied Pharmacology, vol. 196, pp. 396–403, 2004.
[3] C.H. Tseng, C.K. Chong, C.J. Chen, and T.Y. Tai, “Dose-response
relationship between peripheral vascular disease and ingested inorganic
arsenic among residents in Blackfoot disease endemic villages in
Taiwan.” Atherosclerosis, vol. 120, pp. 125–133, 1996.
[4] C.J. Chen, Y.M. Hsueh, M.S. Lai, M.P. Shyu, S.Y. Chen, M.M. Wu,
T.L. Kuo, and T.Y. Tai, “Increased prevalence of hypertension and long
term arsenic exposure.” Hypertension, vol. 25, pp. 53–60, 1995.
[5] P.P. Simeonova, and M.I. Luster, “Arsenic and atherosclerosis.”
Toxicology and Applied Pharmacology, vol. 198, pp. 444–449, 2004.
[6] R. Iffland, D. Seiler, G. Hans, A. Siegel, and H. Siegal, “Handbook on
metals in clinical and analytical chemistry.” New York: Marcel Dekkar,
Inc, 1994, pp. 237–253.
[7] Z. Li, F. Piao, S. Liu, Y. Wang, and S. Qu, “Subchronic exposure to
arsenic trioxideinduced oxidative DNA damage in kidney tissue of
mice.” Experimental and Toxicologic Pathology, vol. 62, pp. 543–547,
2010.
[8] G.K. Harris, and X. Shi, “Signalling by carcinogenic metals and metalinduced
reactive oxygen species.” Mutation Research, vol. 533, pp. 183–
200, 2003.
[9] G. Concha, G. Vogler, D. Lezcano, B. Nermell, and M. Vahter,
“Exposure to inorganic arsenic metabolites during early human
development.” Toxicology Sciences, vol. 44, pp. 185–90, 1998.
[10] V. Devesa, B.M. Adair, J. Liu, M.P. Waalkes, B.A. Diwan, M. Styblo,
and D.J. Thomas, “Arsenicals in maternal and foetal mouse tissues after
gestational exposure to arsenite.” Toxicology, vol. 224, pp. 147–55,
2006.
[11] V.H. Ferm, and S.J. Carpenter, “Malformations induced by sodium
arsenate.” Journal of Reproduction and Fertility, vol. 17, pp. 199-201,
1967.
[12] R.D. Hood, “Effects of sodium arsenite on foetal development.”
Environmental Contamination and Toxicology, vol. 7, pp. 216-222,
1972.
[13] A.R. Beaudoin, “Teratogenicity of sodium arsenate in rats.” Teratology,
vol. 10, pp. 153-158, 1974.
[14] M.P. Waalkes, J.M. Ward, J. Liu, and B.A. Diwan, “Transplacental
carcinogenicity of inorganic arsenic in the drinking water: induction of
hepatic, ovarian, pulmonary, and adrenal tumors in mice.” Toxicol Appl
Pharmacol, vol. 186, pp. 7–17, 2003.
[15] M.P. Waalkes, J. Liu, J.M. Ward, D.A. Powell, and B.A. Diwan,
“Urogenital carcinogenesis in female CD1 mice induced by in utero
arsenic exposure is exacerbated by postnatal diethylstilbestrol
treatment.” Cancer Research, vol. 66, pp. 1337–1345, 2006.
[16] A.H. Smith, G. Marshall, Y. Yuan, C. Ferreccio, J. Liaw, E.O. von, C.
Steinmaus, M.N. Bates, and S. Selvin, “Increased mortality from lung
cancer and bronchiectasis in young adults after exposure to arsenic in
utero and in early childhood.” Environmental Health Perspectives, vol.
114, pp. 1293–1296, 2006.
[17] G. Tournel, V. Gnemmi, and V. Hédouin, “Acute arsenic poisoning:
clinical, toxicological, histopathological, and forensic features.” Journal
of Forensic Sciences, vol. 56, pp. 275–279, 2011.
[18] J.W.E. Harrison, E.W. Packman, and D.D. Abbott, “Acute oral toxicity
and chemical and physical properties of arsenic trioxides.” American
Medical Association Archives of Industrial Health, vol. 17, pp. 118-123,
1958.
[19] K.L. Fishbeck, and K.M. Rasmussen, “Effects of repeated cycles on
maternal nutritional status, lactational performance and litter growth in
ad libitum-fed and chronically food-restricted rats.” The Journal of
Nutrition, vol. 117, pp. 1967–1975, 1987.
[20] H.H. Draper, and M. Hadley, “Malondialdehyde determination as index
of lipid peroxidation.” Methods in Enzymology, vol. 86, pp. 421-431,
1990.
[21] C. Beauchamp, and I. Fridovich, “Superoxide dismutase: improved
assays and an assay applicable to acrylamide gel.” Analytical
Biochemistry, vol. 44, pp. 276–287, 1971.
[22] H. Aebi, “Catalase in vitro.” Methods in Enzymology, vol. 105, pp. 121-
126, 1984.
[23] L. Flohe, and W.A. Gunzler, “Assays of glutathione peroxidase.”
Method Enzymol, vol. 105, pp. 114-121, 1984.
[24] G.L. Ellman, “Tissue sulfhydryl groups.” Archives of Biochemistry and
Biophysics, vol. 82, pp. 70-77, 1959.
[25] D.J. Jollow, J.R. Mitchell, N. Zampaglione, and J.R. Gillette,
“Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic
metabolite.” Pharmacology, vol. 11, pp. 151-169, 1974.
[26] C. Watanabe, T. Inaoka, T. Mastui, K. Ishigaki, N. Murayama, and R.
Ohtsuka. Effects of arsenic on younger generations. Journal of
Environmental Science and Health, vol. 38, pp. 129-139, 2003.
[27] D.N. Guha Mazumder, “Effect of chronic intake of arsenic contaminated
water on liver.” Toxicology and Applied Pharmacology, vol. 206, pp.
169–175, 2005.
[28] M. Messarah, F. Klibet, A. Boumendjel, C. Abdennour, N. Bouzerna,
M.S. Boulakoud, and A. El Feki, “Hepatoprotective role and antioxidant
capacity of selenium on arsenic-induced liver injury in rats.”
Experimental and Toxicologic Pathology, vol. 64(3):pp. 167-74, 2012.
[29] N.J. Chinoy, and M.R. Memon, “Beneficial effects of some vitamins and
calcium on fluoride and aluminium toxicity on gastrocnemius muscle
and liver of male mice.” Fluoride, vol. 34, pp. 21–33, 2001.
[30] S. Pal, and A.K. Chatterjee, Protective effect of N-acetylcysteine against
arsenic-induced depletion in vivo of carbohydrate.” Drug and Chemical
Toxicology, vol. 27, pp. 179–189, 2004.
[31] S. Pal, and A.K. Chatterjee, “Prospective protective role of melatonine
against arsenic-induced metabolic toxicity in Wistar rats.” Toxicology,
vol. 208, pp. 25-33, 2005.
[32] Y. Hu, L. Su, and E.T. Snow, “Arsenic toxicity is enzyme specific and
its effects on ligation are not caused by the direct inhibition of DNA
repair enzymes.” Mutation Research, vol. 408, pp. 203–218, 1998.
[33] E. Lenartowicz, “A complex effect of arsenite on the formation of alphaketoglutarate
in rat liver mitochondria.” Archives of Biochemistry and
Biophysics, vol. 283, pp. 388–396, 1990.
[34] A.K. Patlolla, C. Barnes, C. Yedjou, V.R. Velma, and P.B. Tchounwou,
“Oxidative stress, DNA damage, and antioxidant enzyme activity
induced by hexavalent chromium in sprague-dawley rats.”
Environmental Toxicology, vol. 24, pp. 66-73, 2009.
[35] F.M. El-Demerdash, M.I. Yousef, and F.A. Elaswad, “Biochemical
study on the protective role of folic acid in rabbits treated with
chromium (VI).” Journal of Environmental Science and Health, Part B,
vol. 41, pp. 731–746, 2006.
[36] C.L. Gaskill, L.M. Miller, J.S. Mattoon, W.E. Hoffmann, S.A. Burton,
H.C.J. Gelens, S.L. Ihle, J.B. Miller, D.H. Shaw, and A.E. Cribb, “Liver
histopathology and liver serum alanine aminotransferase and alkaline
phosphatase activities in epileptic dogs receiving Phenobarbital.”
Veterinary Pathology, vol. 42, pp. 147-160, 2005.
[37] A. Albores, M.E. Cebria´n, P.H. Bach, J.C. Connelly, R.H. Hinton and
J.M. Bridges, “Sodium arsenite induced alterations in bilirubin excretion
and heme metabolism.” Journal of Biochemical Toxicology, vol. 4, pp.
73–78, 1989.
[38] A. Hernandez-Zavala, L.M. Del Razo, C. Aguilar, G.G. Garcia-Vargas,
V.H. Borja, and M.E. Cebrian, “Alteration in bilirubin excretion in
individuals chronically exposed to arsenic in Mexico.” Toxicology
Letters, vol. 99, pp. 79-84, 1998.
[39] S. Das, A. Santra, S. Lahiri, and D.N. Guha Mazumder, “Implications of
oxidative stress and hepatic cytokine (TNF-alpha and IL-6) response in
the pathogenesis of hepatic collagenesis in chronic arsenic toxicity.”
Toxicology and Applied Pharmacology, vol. 204, pp. 18–26, 2005.
[40] S.X. Liu, M. Athar, I. Lippai, C. Waldren, and T.K. Hei, “Induction of
oxyradicals by arsenic: implication for mechanism of genotoxicity.”
Proceedings of the National Academy of Sciences USA, vol. 98, pp.
1643–1648, 2001.
[41] K.T. Yamanaka, R. Sawamura, A. Hasegawa, and S. Okada, “Induction
of DNA damage by dimethyl arsine, a main metabolite of inorganic
arsenics, is for the major part due to its peroxyl radical.” Biochemical
and Biophysical Research Communications, vol. 168, pp. 58–64, 1989.
[42] N.J. Chinoy, and S.D. Shah, “Biochemical effects of sodium fluoride
and arsenic trioxide and their reversal in brain of mice.” Fluoride, vol.
37, pp. 80-87, 2004.
[43] S. Maiti, and A.K. Chatterjee, “Effects in levels of glutathione and some
related enzymes in tissues after an acute arsenic exposure in rats and
their relationship to dietary protein deficiency.” Archives of Toxicology,
vol. 75, pp. 531-537, 2001.
[44] S.J.S. Flora, “Arsenic-induced oxidative stress and its reversibility.”
Free Radical Biology and Medicine, vol. 51, pp. 257–281, 2011.
[45] G. Saxena, and S.J.S. Flora, “Lead induced oxidative stress and
haematological alterations and their response to combined
administration of calcium disodium EDTA with a thiol chelator in rats.”
Journal of Biochemical and Molecular Toxicology, vol. 18, pp. 221–
233, 2004.
[46] R. Gupta, G.M. Kannan, M. Sharma, and S.J.S. Flora, “Therapeutic
effects of Moringa oleifera on arsenic-induced toxicity in rats.”
Environmental Toxicology and Pharmacology, vol. 20, pp. 456-464,
2005.
[47] M.N. Kirkman, and G.F. Gaetani, “Catalase: a tetrameric enzyme with
four tightly bound molecules of NADPH. Proceedings of the National
Academy of Sciences USA, vol. 81, pp. 4343–4347, 1984.
[48] F. Nielson, “Other trace elements.” In: Ziegler, E.E., Filer, L.J. (Eds.),
Present Knowledge in Nutrition, seventh ed. Washington, DC: ILSI
Press, 1995, pp. 353–377.
@article{"International Journal of Biological, Life and Agricultural Sciences:69188", author = "H. Bouaziz and N. Soudania and M. Essafia and I. Ben Amara and A. Hakim and K. Jamoussi and Km. Zeghal and N. Zeghal", title = "Hepatotoxicity Induced by Arsenic Trioxide in Adult Mice and Their Progeny", abstract = "In this investigation, we have evaluated the effects of
arsenic trioxide on hepatic function in pregnant and lactating Swiss
albino mice and their suckling pups. Experiments were carried out on
female mice given 175 ppm As2O3 in their drinking water from the
14th day of pregnancy until day 14 after delivery. Our results showed
a significant decrease in plasma levels of total protein and albumin,
cholesterol and triglyceride in As2O3 treated mice and their pups. The
hyperbilirubinemia and the increased plasma total alkaline
phosphatase activity suggested the presence of cholestasis.
Transaminase activities as well as lactate deshydrogenase activity in
plasma, known as biomarkers of hepatocellular injury, were elevated
indicating hepatic cells’ damage after treatment with As2O3.
Exposure to arsenic led to an increase of liver thiobarbituric acid
reactive substances level along with a concomitant decrease in the
activities of superoxide dismutase, catalase and glutathione
peroxidase and in glutathione.
", keywords = "Antioxidant status, arsenic trioxide, hepatotoxicity,
mice, oxidative stress.", volume = "9", number = "3", pages = "250-6", }
