The effect of long-term streptozotocin-induced diabetes on the hepatotoxicity of bromobenzene and carbon tetrachloride and hepatic biotransformation in rats

Watkins, John B.; Sanders, Ruth A.; Beck, Lyle V.

doi:10.1016/0041-008x(88)90133-0

Cited by 31 publications

(15 citation statements)

References 32 publications

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“…Several studies in DB rats indicate that both type 1 and type 2 diabetes are predisposing factors for hepatic sensitivity to drugs and toxicants (El-Hawari and Plaa, 1983;Grant and Duthie, 1988;Watkins et al, 1988;Wang et al, 2000a;Sawant et al, 2004). However, marked species difference in hepatotoxic sensitivity exists between type 1 DB rats and mice (Shankar et al, 2003a;Wang et al, 2000a).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies conducted in type 1 DB rats and mice to test hepatotoxic sensitivity clearly indicate that type 1 DB rats are sensitive (El-Hawari and Plaa, 1983;Grant and Duthie, 1988;Watkins et al, 1988;Wang et al, 2000a), whereas the type 1 DB mice are resistant to hepatotoxicity induced by several dissimilar hepatotoxicants (Shankar et al, 2003a,c), indicating species difference in hepatotoxic sensitivity. Studies by Wang et al (2000aWang et al ( ,b, 2001 in type 1 DB rats indicated that inhibited compensatory tissue repair plays a determining role in the final toxic outcome after thioacetamide (TA) administration.…”

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confidence: 99%

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Protective Effect of Type 2 Diabetes on Acetaminophen-Induced Hepatotoxicity in Male Swiss-Webster Mice

Sawant

Dnyanmote²,

Mitra³

et al. 2005

J Pharmacol Exp Ther

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Type 2 diabetic (DB) mice exposed to CCl 4 (LD 50 ϭ 1.25 ml/kg), acetaminophen (LD 80 ϭ 600 mg/kg; APAP), and bromobenzene (LD 80 ϭ 0.5 ml/kg) i.p. yielded 30, 20, and 20% mortality, respectively, indicating hepatotoxic resistance. Male SwissWebster mice were made diabetic by feeding high fat and administrating streptozotocin (120 mg/kg i.p.) on day 60. On day 71, time-course studies after APAP (600 mg/kg) treatment revealed identical initial liver injury in non-DB and DB mice, which progressed only in non-DB mice, resulting in 80% mortality. The hypothesis that decreased APAP bioactivation, altered toxicokinetics, and/or increased tissue repair are the underlying mechanisms was investigated. High-performance liquid chromatography analysis revealed no difference in plasma and urinary APAP or detoxification of APAP via glucuronidation between DB and non-DB mice. Hepatic CYP2E1 protein and activity, glutathione, and [14 C]APAP covalent binding did not differ between DB and non-DB mice, suggesting that lower bioactivation-based injury is not the mechanism of decreased hepatotoxicity in DB mice. Diabetes increased cells in S phase by 8-fold in normally quiescent liver of these mice. Immunohistochemistry revealed overexpression of calpastatin in the newly dividing/divided cells, explaining inhibition of hydrolytic enzyme calpain in perinecrotic areas and lower progression of APAP-initiated injury in the DB mice. Antimitotic intervention of diabetes-associated cell division with colchicine before APAP administration resulted in 70% mortality in APAPtreated colchicine-intervened DB mice. These studies suggest that advancement of cells in the cell division cycle and higher tissue repair protect DB mice by preventing progression of APAP-initiated liver injury that normally leads to mortality.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Protective Effect of Type 2 Diabetes on Acetaminophen-Induced Hepatotoxicity in Male Swiss-Webster Mice

Sawant

Dnyanmote²,

Mitra³

et al. 2005

J Pharmacol Exp Ther

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“…Hepatotoxicity of model hepatotoxicants is increased in type 1 DB rats (Hanasono et al, 1975;Watkins et al, 1988;Mak and Ko, 1997;Maritim et al, 2000;Wang et al, 2000). We wanted to test whether our model could be used to investigate potential high sensitivity to hepatotoxicants due to type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Severe life-threatening liver injuries are not uncommon in diabetic patients receiving medication, including antidiabetic drugs such as troglitazone and acarbose (Ballet, 1977;Andrade et al, 1996;Neuschwander-Tetri et al, 1998). Evidence with animal studies suggest that type 1 diabetic rats are more sensitive to model hepatotoxicants such as thioacetamide (TA) and CCl 4 (Watkins et al, 1988;Mak and Ko, 1997;Wang et al, 2000). Increased hepatic biotransformation enzymes (Watkins et al, 1988), decreased detoxification systems (Mak and Ko, 1997), and inhibited tissue repair (Wang et al, 2000) are examples of mechanisms that lead to higher sensitivity.…”

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confidence: 99%

“…Evidence with animal studies suggest that type 1 diabetic rats are more sensitive to model hepatotoxicants such as thioacetamide (TA) and CCl 4 (Watkins et al, 1988;Mak and Ko, 1997;Wang et al, 2000). Increased hepatic biotransformation enzymes (Watkins et al, 1988), decreased detoxification systems (Mak and Ko, 1997), and inhibited tissue repair (Wang et al, 2000) are examples of mechanisms that lead to higher sensitivity. Although there is ample evidence that type 1 diabetes increases sensitivity to hepatotoxicants, such sensitivity of type 2 diabetes has not been investigated.…”

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Potentiation of Carbon Tetrachloride Hepatotoxicity and Lethality in Type 2 Diabetic Rats

Sawant

Dnyanmote²,

Shankar³

et al. 2003

J Pharmacol Exp Ther

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There is a need for well characterized and economical type 2 diabetic model that mimics the human disease. We have developed a type 2 diabetes rat model that closely resembles the diabetic patients and takes only 24 days to develop robust diabetes. Nonlethal doses of allyl alcohol (35 mg/kg i.p.), CCl 4 (2 ml/kg i.p.), or thioacetamide (300 mg/kg i.p.) yielded 80 to 100% mortality in diabetic rats. The objective of the present study was to investigate two hypotheses: higher CCl 4 bioactivation and/or inhibited compensatory tissue repair were the underlying mechanisms for increased CCl 4 hepatotoxicity in diabetic rats. Diabetes was induced by feeding high fat diet followed by a single dose of streptozotocin on day 14 (45 mg/kg i.p.) and was confirmed on day 24 by hyperglycemia, normoinsulinemia, and oral glucose intolerance. Time course studies (0 -96 h) of CCl 4 (2 ml/kg i.p.) indicated that although initial liver injury was the same in nondiabetic and diabetic rats, it progressed only in the latter, culminating in hepatic failure, and death. Hepatomicrosomal CYP2E1 protein and activity, lipid peroxidation, glutathione, and 14 CCl 4 covalent binding to liver tissue were the same in both groups, suggesting that higher bioactivation-based injury is not the mechanism. Inhibited tissue repair resulted in progression of injury and death in diabetic rats, whereas in the nondiabetic rats robust tissue repair resulted in regression of injury and survival after CCl 4 administration. These studies show high sensitivity of type 2 diabetes to model hepatotoxicants and suggest that CCl 4 hepatotoxicity is potentiated due to inhibited tissue repair.Several animal models resembling type 2 diabetes either occur spontaneously or can be induced experimentally. Most of the commonly used models of type 2 diabetes are genetic and have the disadvantage of prohibitive costs, unavailability, and failure to represent etiology of human disease. Consumption of high fat diet leads to insulin resistance and is considered to be a major predisposing factor for type 2 diabetes (Kraegen et al., 1986). Models based on high fat diet take 3 months or longer to develop diabetes and yield only moderate hyperglycemia (Surwit et al., 1988;Pascoe et al., 1992;Reed et al., 2000). Thus, there is a need for a robust type 2 diabetes model.To address this need, we have refined and characterized an existing model based on high fat diet and a single dose of streptozotocin (STZ, 45 mg/kg i.p.). The principle behind the development of type 2 diabetes is simple. High fat diet elicits insulin resistance, and the rats maintain normoglycemia due to compensatory hyperinsulinemia. Administration of STZ (45 mg/kg i.p.) decreases insulin levels, destroying a population of pancreatic ␤-cells such that the insulin-resistant rats are now unable to maintain normal glucose levels and develop hyperglycemia, even though insulin levels in these rats are comparable with normal diet-fed normoglycemic rats. This is exactly what is seen in human diabetes where insulin res...

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The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs

Mashayekhi‐Sardoo

Mohammadpour

Nomani

et al. 2019

Journal Cellular Physiology

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Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Cellular mechanisms of hyperglycemia and chemotherapy efficacy may be different depending upon the particular cancer type and the condition of the patient. This review evaluates the effect of DM on the pharmacokinetic, pharmacodynamic, and adverse drug reactions of commonly used anticancer drugs such as cisplatin, methotrexate, paclitaxel, doxorubicin, and adriamycin in both clinical and animal models. A literature search was conducted in scientific databases including Web of Science, PubMed, Scopus, and Google Scholar including the relevant keywords. The results of the effectiveness of anticancer therapies in patients with DM are, however, inconsistent because DM can negativelyimpact multiple diverse entities including nerves and vascular structures, insulin-like growth factor 1, the function of the innate immune system, drug pharmacokinetics, the expression levels of hepatic CYP 450 , Mdr 1b and enzymes that then lead to drug toxicity. However, in a few circumstances, DM led to attenuation of the toxicity of anticancer drugs secondary to attenuation of the energy-dependent renal uptake process. Overall, the impact of DM on patients with cancer is variable because of the diverse types of cancers and the spectrum of anticancer drugs. With respect to the evidence for cancer involvement in DM pathophysiology and the response to anticancer treatment in patients with DM, many questions still remain and further clinical trials are needed.

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The effect of long-term streptozotocin-induced diabetes on the hepatotoxicity of bromobenzene and carbon tetrachloride and hepatic biotransformation in rats

Cited by 31 publications

References 32 publications

Protective Effect of Type 2 Diabetes on Acetaminophen-Induced Hepatotoxicity in Male Swiss-Webster Mice

Protective Effect of Type 2 Diabetes on Acetaminophen-Induced Hepatotoxicity in Male Swiss-Webster Mice

Potentiation of Carbon Tetrachloride Hepatotoxicity and Lethality in Type 2 Diabetic Rats

The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs

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