Alteration of drug metabolizing enzymes in sulphite oxidase deficiency

Abstract

The aim of this study was to investigate the possible effects of sulphite oxidase (SOX, E.C. 1.8.3.1) deficiency on xenobiotic metabolism. For this purpose, SOX deficiency was produced in rats by the administration of a low molybdenum diet with concurrent addition of 200 ppm tungsten to their drinking water. First, hepatic SOX activity in deficient groups was measured to confirm SOX deficiency. Then, aminopyrine N-demethylase, aniline 4-hydroxylase, aromatase, caffeine N-demethylase, cytochrome b5 reductase, erythromycin N-demethylase, ethoxyresorufin O-deethylase, glutathione S-transferase, N-nitrosodimethylamine N-demethylase and penthoxyresorufin O-deethylase activities were determined to follow changes in the activity of drug metabolizing enzymes in SOX-deficient rats. Our results clearly demonstrated that SOX deficiency significantly elevated A4H, caffeine N-demethylase, erythromycin N-demethylase and N-nitrosodimethylamine N-demethylase activities while decreasing ethoxyresorufin O-deethylase and aromatase activities. These alterations in drug metabolizing enzymes can contribute to the varying susceptibility and response of sulphite-sensitive individuals to different drugs and/or therapeutics used for treatments.

An update to the toxicological profile for water-soluble and sparingly soluble tungsten substances

“…Rats exposed via drinking water or gavage to several concentrations of ST ranging from 28 to 100 mg/kg/d for 14 d to 6 weeks, showed a reduction in enzymatic activities of molybdenum-dependent enzymes such as xanthine oxidase (XO), XDH, and SO, in the kidney, intestine, liver, plasma, and erythrocytes ( Weber et al 2008 , Herken et al 2009 , Ozturk et al 2010 , Aydemir et al 2012 , Tutuncu et al 2012 ). Mice liver AO activity was reduced by 45% when treated via drinking water for 14 d with ST at approximately 170 mg/kg/d ( Swenson and Casida 2013 ).…”

Short Review of Sulphites as Food Additives

“…Sulphites have been implicated as initiators of asthmatic reactions in a small subset of sensitive individuals of the asthmatic population [2]. Adverse reactions, including anaphylactic reactions, dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea, have been reported in those individuals [29]. The mechanism of action of sulphites in asthmatic reactions is not established, and various studies have proposed different possible mechanisms.…”

Sulfites and Hypersensitivity Reactions

“…Bu yetersizliğin ileri derecelerinde, göz lenslerinde bozukluk ile mental ve fiziksel retardasyona neden olan nörolojik anomaliler gözlenmektedir. Sıçanlara, Tungsten içerikli bir diyet verildiğinde, molibdenin tungstenle yer değiştirdiği ve bu şekilde sülfit oksidaz enzim aktivitesinin azaldığı saptanmıştır (6,9,10). Sağlıklı insanlarda, sülfitlerin sindirimi sonucu metabolizmada bisülfit oluşumu ile sülfit oksidaz aktivitesi yoluyla sülfitin metabolize olması arasında sürekli bir etkileşim bulunmaktadır.…”

“…Sonuçlarda, SOX eksikliğinin etoksiresorufin O-ditilaz ve aromataz aktivitelerini azaltırken, A4H, kafein N-demetilaz, eritromisin N-demetilaz ve N-nitrosodimetilamin N-demetilaz faaliyetlerini ise önemli ölçüde artırdığı gösterilmiştir. İlaç metabolize eden enzimlerdeki bu değişikliklerin farklı duyarlılık ve sülfit duyarlı bireylerin tedaviler için kullanılan farklı ilaçlar ve/veya terapötiklere yanıtı açısından katkıda bulunabileceği belirtilmiştir (10). Sülfit oksidaz eksikliği, sülfit hassasiyeti olan bireylerde öncü hücre doku kültürleri ile belirlenmiş ve doku etkileşiminin daha düşük olduğu saptanmıştır.…”