Evaluation of Antioxidant Supplementation on Redox Unbalance in Hyperthyroid Cats Treated with Methimazole: A Blinded Randomized Controlled Trial

Abstract

Methimazole (MMI) is often the selected medical treatment for feline hyperthyroidism. However, the onset of MMI-related side effects (MMI-SE) is likely caused by oxidative stress. This study evaluated the dietary supplementation of selected antioxidants in hyperthyroid cats receiving MMI, to reduce MMI-SE. Thirty hyperthyroid client-owned cats were randomly allocated in group M (MMI + placebo) or group M+A (MMI + antioxidants). At different time-points from the enrolment (ET) to the end of the trial (FT), the following information was recorded: clinical findings, complete blood count, serum biochemical parameters, urinalysis, total plasma thyroxine concentrations, determinable reactive oxygen metabolites (dROMs), OXY-adsorbent test values, and oxidative stress index (OSi) values, and MMI-SE. dROMs and OSi values significantly increased from ET to FT in group M and were significantly higher in group M than in group M+A at FT. Likewise, OXY-absorbent test values were significantly higher in group M+A than in group M at FT. Moreover, the occurrence rate of MMI-SE in group M+A was lower than in group M. In conclusion, our results show that the dietary supplementation of antioxidants in hyperthyroid cats receiving MMI exerts a protective effect against oxidative stress, likely contributing to the reduction of MMI-SE.

Management of Feline Hyperthyroidism and the Need to Prevent Oxidative Stress: What Can We Learn from Human Research?

“…It should also be considered that dietary management can possibly exert a synergistic effect with the pharmacological treatment (synergistic scope). In fact, administration of dietary antioxidants to hyperthyroid patients receiving oral antithyroid drugs could possibly ameliorate their clinical outcome and reduce MMI-related side-effects, as already demonstrated in human and animal studies [ 5 , 11 ]. According to the authors, the pursuit of a dietary and synergistic scope plays a crucial role in the “multimodal approach to the hyperthyroid cat” that is proposed in the present review.…”

“…Unfortunately, oral anti-thyroid drugs are not free from side-effects. More to the point, administering a pill to a cat, once or twice daily for a life-long period, can be tricky and waste money [ 11 ]. Transdermal application of a pluronic-lecithin organogel (PLO) containing MMI has been suggested as an alternative treatment regimen; Hill et al [ 29 ] recently demonstrated that a novel lipophilic formulation was as effective and safe as twice daily oral CMZ in the treatment of cats with hyperthyroidism.…”

“…Moreover, some studies underline the role of oxidative disturbances in the initiation of Graves’ disease (GD), Plummer’s disease and hyperthyroidism-induced damage, such as thyrotoxic myopathy, cardiomyopathy, and Graves’ orbitopathy (GO), [ 7 , 46 , 47 , 48 , 49 ]. However, some contradictions still emerge from a literature review related to studies conducted in animals [ 4 , 5 , 11 ]. Given the above, a summary of results deriving from clinical and experimental trials on hyperthyroid subjects, focused on evaluating their redox unbalance, will be presented in the following sections.…”

“…Feline studies evaluating OS in course of thyrotoxicosis are scattered [ 5 , 11 , 24 ]. In 2009 Viviano et al, [ 53 ] quantified erythrocyte reduced glutathione, plasma cysteine, and plasma ascorbate in clinically ill cats and dogs.…”

“…Metabolic oxidation has been correlated, both in hyperthyroid humans and cats, with signs and symptoms of the disease [ 5 ]; the decrease in antioxidant defenses and therefore the boost in oxidative stress can also be considered a risk factor for several idiosyncratic drug toxicity syndromes to anti-thyroid drugs, such as methimazole [ 6 , 7 ]. Achievement of euthyroidism results in normalization of redox markers [ 8 , 9 , 10 ], while the severity of clinical signs and the occurrence of methimazole-adverse reactions could be mitigated by the simultaneous administration of dietary supplements (e.g., antioxidants) [ 11 , 12 , 13 ]. The aim of this work is to (1) describe current therapeutic options in course of feline hyperthyroidism, with particular emphasis on nutritional management and (2) to summarize the state of the art relationship between the dietary supplementation of selected antioxidant molecules (such as curcumin, quercetin, resveratrol and vitamin E) and the reduction of methimazole side-effects in humans and to identify a possible rationale for this approach also in FHT.…”