Pentoxifylline prevents the meglumine antimonate-induced renal toxicity in rats, but not that induced by the inorganic antimony pentachloride

Moura, Flávio José Dutra de; Leal, Pushkin Pires; Furtado, Rogério de Souza; Muniz‐Junqueira, Maria Imaculada; Veiga, Joel Paulo Russomano

doi:10.1016/j.tox.2007.09.032

Cited by 11 publications

(7 citation statements)

References 30 publications

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“…30 Tubular necrosis and decreased creatinine clearance have also been reported. 29 Interestingly, consistent with our results before adjustment for the other metals, decreased serum creatinine was observed in a dose-related manner in rats exposed to trivalent antimony salt via drinking water over a 90-day study period. 31 Route of administration may be relevant in animal data; nephrotoxicity from antimony potassium tartrate administered intraperitoneally but not via drinking water has been reported.…”

Section: Discussionsupporting

confidence: 90%

“…4 Nephrotoxicity is a side effect of pentavalent antimony use in the treatment of parasitic diseases, such as leishmaniasis. 29 Increased serum creatinine, blood urea nitrogen and proteinuria have been observed in animal models following 30 days of intramuscular injections with pentavalent antimony compounds. 30 Tubular necrosis and decreased creatinine clearance have also been reported.…”

Section: Discussionmentioning

confidence: 99%

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Associations of multiple metals with kidney outcomes in lead workers

et al. 2012

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Objectives Environmental exposure to multiple metals is common. A number of metals cause nephrotoxicity with acute and/or chronic exposure. However, few epidemiologic studies have examined the impact of metal co-exposure on kidney function. Therefore, we evaluated associations of antimony and thallium with kidney outcomes and assessed the impact of cadmium exposure on those associations in lead workers. Methods Multiple linear regression was used to examine associations between ln-urine thallium, antimony and cadmium levels with serum creatinine- and cystatin-C-based glomerular filtration measures, and ln-urine N-acetyl-β-D-glucosaminidase (NAG). Results In 684 participants, median urine thallium and antimony were 0.39 and 0.36 μg/g creatinine, respectively. After adjustment for lead dose, urine creatinine, and kidney risk factors, higher ln-urine thallium was associated with higher serum creatinine- and cystatin-C-based estimates of glomerular filtration rate (eGFR); associations remained significant after adjustment for antimony and cadmium (regression coefficient for serum creatinine-based eGFR = 5.2 mL/min/1.73 m2; 95% confidence interval = 2.4, 8.0). Antimony associations with kidney outcomes were attenuated by thallium and cadmium adjustment; thallium and antimony associations with NAG were attenuated by cadmium. Conclusions Urine thallium levels were significantly associated with both serum creatinine- and cystatin-C-based glomerular filtration measures in a direction opposite that expected with nephrotoxicity. Given similarities to associations recently observed with cadmium, these results suggest that interpretation of urine metal values, at exposure levels currently present in the environment, may be more complex than previously appreciated. These results also support multiple metal analysis approaches to decrease the potential for inaccurate risk conclusions.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Associations of multiple metals with kidney outcomes in lead workers

et al. 2012

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“…There are several potential limitations of the present study that should be addressed. Firstly, pentoxifylline has been found to have novel biochemical effects, including the alleviation of renal vasoconstriction ( 23 ), reduction of oxidative stress and modulation of inflammatory responses ( 24 ). These properties may also be used to prevent CIAKI as proposed by Roozbeh et al ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Preventive effect of pentoxifylline on contrast-induced acute kidney injury in hypercholesterolemic rats

Yang

Duan

Pan

et al. 2014

Experimental and Therapeutic Medicine

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Oxidative stress is an important mechanism of contrast-induced acute kidney injury (CIAKI). The optimal strategy to prevent CIAKI remains unclear. The aim of the present study was to assess the effect of pentoxifylline, a nonspecific phosphodiesterase inhibitor, on the prevention of CIAKI. A total of 32 healthy male Sprague-Dawley rats were randomly divided into normal dietary group (NN; n=8) and a high cholesterol-supplemented dietary group (HN; 4% cholesterol and 1% cholic acid; n=24). At the end of eight weeks, the rats in the high cholesterol diet group were randomly divided into three subgroups (n=8 in each group). CIAKI was induced in two of the subgroups via intravenous injection of the radiocontrast media iohexol (10 ml/kg). Pentoxifylline (50 mg/kg) was administered to one of the iohexol-treated groups via intraperitoneal injection 12 h prior to and following contrast media (CM) injection. Kidney function parameters and oxidative stress markers were then measured. The renal pathological changes were evaluated using hematoxylin and eosin staining and scored semi-quantitatively. In iohexol-injected rats, serum creatinine (Scr), renal pathological scores, renal malondialdehyde (MDA) content, renal NADPH oxidase activity, fractional excretion of sodium (FENa%) and fractional excretion of potassium (FEK%) were significantly increased (P<0.01). The Scr, histologic scores, renal MDA content, NADPH oxidase activity, FENa% and FEK% in the rats treated with pentoxifylline prior to iohexol were observed to be reduced compared with those in rats treated with iohexol alone (P<0.01). This suggests that pentoxifylline significantly attenuates renal injuries, including tubular necrosis and proteinaceous casts induced by CM. It may be concluded that pentoxifylline protected the renal tissue from the nephrotoxicity induced by low-osmolar CM via an antioxidant effect.

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“…Similarly, pentoxifylline (a methylxanthine) has been investigated in the treatment of CL, based on its inhibition of nuclear factor kappa beta (NF-kβ), TNF-α, and intercellular adhesion molecule 1 (ICAM-1) 8,9 , as well as its nephroprotective effect when combined with antimonials 10 . These immunomodulatory effects may help to regulating patients' exacerbated and inefficient intracellular immune response to parasites, and subsequently reduce tissue infl ammation.…”

mentioning

confidence: 99%

“…Pentoxifylline has also been shown to have a nephroprotective effect when combined with pentavalent antimonials 10 . A treatment scheme, preferably using oral administration, is necessary, especially in Brazil, where CL is common in the North and Northeast regions.…”

mentioning

confidence: 99%

Effectiveness of miltefosine-pentoxifylline compared to miltefosine in the treatment of cutaneous leishmaniasis in C57Bl/6 mice

Santarem

Greggianin

Debastiani

et al. 2014

Rev. Soc. Bras. Med. Trop.

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Introduction:The treatment of leishmaniasis ischallenging, given the diffi culties in drug administration and resistance. Therefore, we chose to test the effi cacy of miltefosine combined with pentoxifylline. Methods: Twenty-seven isogenic C57Bl/6 mice were infected with Leishmania (Leishmania) amazonensis, and equally divided into three groups: miltefosine (200mg/ kg/day), miltefosine (200mg/kg/day) with pentoxifylline (8mg/kg/day), and untreated. Response to treatment was evaluated using paw diameter and parasitological criteria. Results: The number of viable Leishmania reduced signifi cantly within the miltefosine-pentoxifylline group (p < 0.05). Conclusions: There is hope that a viable treatment exists for Leishmania infection.

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Pentoxifylline prevents the meglumine antimonate-induced renal toxicity in rats, but not that induced by the inorganic antimony pentachloride

Cited by 11 publications

References 30 publications

Associations of multiple metals with kidney outcomes in lead workers

Associations of multiple metals with kidney outcomes in lead workers

Preventive effect of pentoxifylline on contrast-induced acute kidney injury in hypercholesterolemic rats

Effectiveness of miltefosine-pentoxifylline compared to miltefosine in the treatment of cutaneous leishmaniasis in C57Bl/6 mice

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