Open Veterinary Journal, (2026), Vol. 16(2): 841-846

Research Article

10.5455/OVJ.2026.v16.i2.8

Assessing the effects of linseed consumption on thyroid hormones and hepatic toxicity in rats drenched with Cordarone overdose

Moayad Mijbil Ubaid¹, Sara Najem Abed², Shaimaa Jabbar³, Hadiya Jumaah Oraibi³ and Shatha Hussein Kadhim^3*

¹Department of Biology, College of Basic Education, University of Sumer, Rifai, Iraq

²Department of Pharmaceutics, College of Pharmacy, University of Kerbala, Karbala, Iraq

³Department of Pharmacology and Toxicology, College of Pharmacy, University of Kerbala, Karbala, Iraq

*Corresponding Author: Shatha Hussein Kadhim. Department of Pharmacology and Toxicology, College of Pharmacy, University of Kerbala, Kerbala, Iraq. Email: shatha.kadhim [at] uokerbala.edu.iq

Submitted: 13/10/2025 Revised: 15/01/2026 Accepted: 25/01/2026 Published: 28/02/2026

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Abstract

Background: Cordarone, a benzofuranic-derivative iodine-rich medication primarily used for tachyarrhythmias, frequently induces alterations in the peripheral metabolism of thyroid hormones, predominantly by inhibiting 5'-deiodinase activity, resulting in elevated serum thyroxine and reverse triiodothyronine (T3) levels, alongside diminished serum T3 concentrations. Overt thyroid dysfunction, which manifests as either Cordarone-induced thyrotoxicosis. Linseed oil or flaxseed oil is a type of oil that comes from seeds. It is one of the oldest oils on the market. Solvent-processed flaxseed oil has been used as a drying oil in painting and varnishing for hundreds of years. Raw oil is utilized as an astringent in fungicidal lotion. It also acts as an insecticide and has some insect-repelling effects.

Aim: The study sought to show the therapeutic effects of linseed oil on biochemical parameters in rats against the toxic effects of Cordarone.

Methods: In this study, we used twenty-four adult male rats and splited into three groups: control group: drenched standard nutrition only. Cordarone group: drenched Cordarone (100 mg/kg/day) orally by gavage. Cordarone + Linseed oil group: rats were drenched with Cordarone (100 mg/kg/day) and linseed oil (3 ml/kg/day) for a month. At the end of this experiment, the rats were scarified and blood samples were taken from the animals for biochemical parameters (ALT, AST, troponin, TSH, T3, and T4).

Results: The data showed the positive effect of linseed in improving the thyroid gland, heart, and liver against the toxic effect of Cordarone.

Conclusion: Linseed had a positive effect against the toxic effects of Cordarone by enhancing hematology parameters. These findings proved benefit of linseed.

Keywords: Biochemical parameters, Cordarone, Linseed oil, Thyroid disorders.

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Introduction

The thyroid gland is an important endocrine gland that looks like a butterfly and is located in the lower portion of the neck. It is located at the front and sides of the trachea, below the larynx. It is important for controlling the BMR, stimulating physical and mental growth, and calcium metabolism (Chaudhary, 2013).

The thyroid gland helps in normal growth and development by maintaining the metabolism of the tissues at the optimal level for normal function. Thyroxine (T4) and triiodothyronine (T3) are the 2 main thyroid hormones. Not enough thyroid hormone is released (hypothyroidism). In contrast, hyperthyroidism occurs when there is excessive release of thyroid hormones (Patton and Thibodeau, 2018). It influences the osteoblast lineage. TH boosts osteoblastic activity (Hofstee et al., 2019). Thyroid hormones increase the basal metabolic rate. It increases the activity of Na+/K+ ATPase genes in different tissues, which makes the body use more oxygen, breathe faster, and get hotter. It can cause lipolysis or lipid synthesis, depending on the metabolic state (Delitala et al., 2019). Some people with hyperthyroidism for a long time have cardiac hypertrophy (Tost et al., 2020). The most prevalent non-neoplastic thyroid lesion is goiter, specifically colloid nodular goiter. Graves’ disease and thyroid cancer are the primary conditions that impair thyroid gland function (Zheng and Niu, 2024; Kamma et al., 2025).

Excessive amounts of thyroid hormones are a condition of hypermetabolic state and hyperfunctioning of the thyroid gland, resulting in elevated T3 and T4 levels. Some symptoms are palpitations, tachycardia, and anxiety. An overactive thyroid, Graves disease (Graves hyperthyroidism), is the most prevalent cause of hyperthyroidism, making up 60%–80% of the patients (Lee and Pearce, 2023).

Cordarone is an antiarrhythmic medicine that is currently used more often. This is because several studies have shown that it might cause adverse effects such as chronic toxicity, mainly in the lungs, liver, and thyroid glands. Furthermore, an elevation in serum creatinine was observed in a few patients (Bayrakçeken et al., 2023). Cordarone, a benzofuranic-derivative iodine-rich medication primarily used for tachyarrhythmias, frequently induces alterations in the peripheral metabolism of thyroid hormones, predominantly by inhibiting 5'-deiodinase activity, resulting in elevated serum T4 and reverse T3 levels, alongside diminished serum T3 concentrations (Bayrakçeken et al., 2023). Overt thyroid dysfunction, which manifests as either Cordarone-induced thyrotoxicosis (AIT) or Cordarone-induced hypothyroidism (AIH), occurs in 14%–18% of patients undergoing long-term treatment. This dysfunction may arise in normal thyroid glands or in those with underlying abnormalities. AIH primarily results from the inability to evade the acute Wolff–Chaikoff effect, and it is associated with concurrent Hashimoto’s thyroiditis in individuals with thyroid autoimmune disorders (Bogazzi et al., 2001).

Cordarone relaxes the smooth muscles that line the walls of blood vessels, lowers peripheral vascular resistance (afterload) (Bulut et al., 2025), and slightly raises the cardiac index after being administered through an IV. This method of administration also slows down the heart’s conduction, which stops and treats arrhythmias (Delitala et al., 2019). Cordarone extends the QRS duration and QT interval. Additionally, the SA (sinoatrial) node’s automaticity decreases as the AV node’s conduction velocity decreases. Likewise, ectopic pacemaker automaticity is suppressed. Cordarone, which contains a lot of iodine and interferes with normal thyroid function, can also cause thyrotoxicosis or hypothyroidism (Mughal et al., 2018).

Linseed oil is the oilseed flax (linseed) (Linum usitatissimum ) from which quality oil comes, and omega-3 fatty acids are the most prized part of it. A thorough biochemical study of linseed oil led to the discovery of its other parts, similar to other medical plants, that may be used to benefit human health (Farag et al., 2021; Ubaid et al., 2025). Linseed oil or flaxseed oil is a type of oil that comes from seeds. It is one of the oldest oils on the market. Solvent-processed flaxseed oil has been used as a drying oil in painting and varnishing for hundreds of years. Raw oil is utilized as an astringent in fungicidal lotion. It also acts as an insecticide and has some insect-repelling effects (Kaithwas and Majumdar, 2013). Oleic acid (12%–30%), linoleic acid (8%–29%), and linolenic acid (35%–67%) are unsaturated fatty acids found in the oil – linseeds because they contain a lot of omega-3 fatty acids. They are necessary for the thyroid gland to function properly; thus, those with hyperthyroidism should consume them. To obtain all the advantages, grind them right before you eat them (White, 2007). There are mixed results regarding how flax seeds affect people with thyroid difficulties. This is because flax seeds contain linolenic acid, which helps with inflammation and balances thyroid hormone imbalances. Flax seeds also provide magnesium and vitamin B-6, which help the thyroid gland function properly, especially in patients with thyroiditis (Ahmed et al., 2021). However, flax seeds are considered one of the things that can make the thyroid gland bigger. They also contain phytate, a type of salt that binds to minerals and salts in the body, such as iodine, selenium, and zinc, which are all needed for the thyroid gland to function and produce the necessary hormones. If these minerals attach to the thyroid gland, it will not work as well, and some people may need to take more T4 (levothyroxine) pills.

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Materials and Methods

Animals

This investigation was conducted at the College of Pharmacy in Karbala University in August 2024. We used 24 healthy adult rats that weighed between 170 and 280 g. The pharmacy college’s animal house provided the animals. Rats were housed in clean plastic cages and were given a conventional laboratory diet. They could drink and eat at any time, and the light and dark cycles were typical. The committee’s local rules for controlling and monitoring animal studies were followed in every way when it came to caring for and treating animals.

Experimental design

In this study, we used twenty-four adult male rats and splited into three groups:

1-control group: drenched standard nutrition only.

2-Cordarone group: drenched Cordarone (100mg/kg/day) orally by gavage.

3-Cordarone+Linseed oil group: rats were drenched with Cordarone (100mg/kg/day) and linseed oil (3ml/kg/day) for month. At the end of this experiment, the rats were scarified and blood samples were taken from them for biochemical parameters (ALT, AST, troponin, TSH,T3, and T4) at the end of this protocol according to Baş (2016).

Statistical analysis

Data were analyzed using the Statistical Package for the Social Sciences program for Windows (Standard version 21). Continuous variables were presented as mean ± SE. The ANOVA test was used to compare the means. The results were considered nonsignificant when the probability of error was >5% (p > 0.05) and significant when the probability of error was 5% (p ≤ 0.05).

Ethical approval

This study was approved by the Scientific and Ethical Committee of the Faculty of Pharmacy, University of Karbala, on September 23, 2024 (Ref:2024An.20). The study was conducted in accordance with the Declaration of Helsinki.

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Results

Liver and heart parameters

Table 1 shows the effect of using linseed oil in improving liver and heart function in rats treated with Cordarone. There was a significant elevation in ALT and AST (62.66 and 120.50, respectively) in the Cordarone group compared to the control group, while these levels were significantly reduced in the linseed and Cordarone groups (44.33 and 98, respectively), and there were no significant changes in the troponin level.

Thyroid hormones

Table 2 shows the effect of linseed oil on the levels of thyroid hormones in rats treated with Cordarone. There was a significant elevation in T4 and TSH levels (54 and 0.098, respectively) and significant decrease in T3 level (0.26) in the Cordarone group compared to control group, the table also revealed that the levels of (T3, T4, TSH) were significantly returned to nearly normal values (0.41, 28.08, 0.044) respectively in Cordarone+ Linseed oil group.

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Discussion

The results of the recent study showed that Cordarone is associated with elevated liver enzymes, particularly aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The explanation of these results is that Cordarone is a lipophilic drug that accumulates mainly in adipose tissue and organs with high blood perfusion, such as the liver. Hepatotoxicity is a relatively uncommon adverse reaction to Cordarone (Lafuente‐Lafuente et al., 2009). AST levels were elevated much more than ALT levels in animals treated with Cordarone, which may be because AST is more abundant in mitochondria than ALT. Because Cordarone causes mitochondrial toxicity, AST levels are often elevated more than ALT levels. This is similar to alcohol-induced liver injury, where mitochondrial damage also leads to a higher AST:ALT ratio (Rabinowich and Shibolet, 2015). Cordarone and its metabolite, desethyl Cordarone, accumulate in the liver due to its lipophilic nature, leading to mitochondrial dysfunction, oxidative stress, and hepatocyte injury. Liver damage can resemble nonalcoholic steatohepatitis with microvesicular and macrovesicular steatosis (Rabinowich and Shibolet, 2015).

Relating to troponin, it was found that there was a non-significant elevation in its level compared to the control. Cardiac troponin is an enzyme and biomarker of myocardial injury in the heart. Cordarone causes structural and functional changes in the myocardium, leading to injury and the release of troponin (Potter et al., 2022). The increasing of troponin levels in patients whom taken Cordarone may belong to the structural and functional changes in the muscles of the heart (Hindricks et al., 2021). This effect may lead to damage to the muscles of the heart and cause troponin release to the blood. For an example, a case report found that the patients taking Cordarone had a ventricular fibrillation leading to subsequent myocardial stress (Hindricks et al., 2021; Jasim et al., 2023). Cordarone can affect the levels of thyroid hormones since it has a similar structure to thyroid hormones, as well as it has high amounts of iodine. This similarity in structure and high amount of iodine may lead to hyperthyroidism or hypothyroidism. Thus, the dysfunction of the thyroid gland leads to myocardial injury (Ursella et al., 2006). The high amounts of iodine often lead to hyperthyroidism (Medic et al., 2022). Thyrotoxicosis caused by Cordarone may lead to an excessive amount of T4 in response to iodine. This usually occurs in people who already have Graves’ disease (Bartalena et al., 2018).

The present study shows that the TSH level was elevated while the T3 level decreased, and this was due to several reasons: Cordarone inhibits 5’-deiodinase, the enzyme responsible for converting T4 into T3, the active thyroid hormone. This leads to higher T4 levels and a transient decrease in T3 levels, and as a negative feedback action, TSH production is elevated over time (Ryan et al., 2025). Cordarone contains 37% iodine, which releases a large iodine load upon metabolism. This temporarily suppresses thyroid hormone synthesis (Wolff–Chaikoff effect), leading to an initial decrease in T3 and T4 levels. The pituitary gland then compensates by increasing TSH secretion (Osafehinti et al., 2020). Cordarone directly affects the pituitary gland, impairing T3 action at the hypothalamus and pituitary level. This reduces the negative feedback response, causing the pituitary gland to secrete more TSH (Cappellani et al., 2023). Cordarone induces hypothyroidism (Cordarone-induced hypothyroidism, CIH), leading to persistently elevated TSH levels. In contrast, Cordarone-induced thyrotoxicosis (AIT) can cause excess thyroid hormone production, sometimes with a compensatory TSH rise in the early phase. Thus, TSH increases with the use of Cordarone. However, persistent abnormalities may indicate underlying thyroid dysfunction, which requires further evaluation (Hernando and Eliana, 2015) .

Recently, the use of medical plants has become more common as they have fewer side effects and a powerful antioxidant effect, especially against hepatotoxicity and nephrotoxicity caused by drugs (Ubaid et al., 2022; Kadhim et al., 2022; Kadhim et al., 2025; Naser et al., 2025). In this study, the results showed that linseed oil has a protective effect on the liver, like many medical plants, when given simultaneously with Cordarone. This may be explained by the fact that linseed oil, also known as flaxseed oil, has been studied for its potential effects on liver health.

Linseed oil’s high content of omega-3 polyunsaturated fatty acids (PUFAs), particularly alpha-linolenic acid (ALA), contributes to its anti-inflammatory properties. Incorporating linseed oil into the diet can reduce liver inflammation and fat accumulation. For instance, a study involving mice fed a high-carbohydrate diet demonstrated that linseed oil impeded or reduced the progression of liver injury, including fatty liver disease, and decreased ALT and AST levels in the context of Cordarone-induced liver injury (Godoy et al., 2022). Many studies indicated that the uses of linseed oil lead to reduce weight due to its constitutes in “nonalcoholic fatty liver” patients and another study showed hepato-protective effect of this plant by reducing liver enzyme, fibrosis, and lowering fat covering liver after twelve weeks of study. El-Sayed (2023) observed a decrease in liver enzymes, fibrosis, and steatosis after 12 weeks of consumption of flaxseed powder. Many studies have proven that omega-3 fatty acids influence antioxidant effects against drug toxicity (Ubaid, 2019).

Table 1. Effect of Cordarone and linseed on liver and heart indicators in male rats.

Table 2. Effect of Cordarone and linseed on thyroid hormones in male rats.

In this study, results show that linseed oil (rich in ALA) normalizes thyroid hormone levels in rats administered an overdose of Cordarone. The omega-3 fatty acids in linseed oil reduce inflammation, which may suppress the compensatory response of the thyroid. PUFAs in linseed oil may further inhibit 5’-deiodinase, reducing the conversion of T4 to T3, thereby worsening hypothyroidism (Shaikh Omar, 2018; Chen et al., 2022). The decrease in thyroid-stimulating hormone (TSH) despite the reduction in T3 and T4 when linseed oil is given may be explained by the following mechanisms: Linseed oil is rich in ALA, an omega-3 fatty acid that can influence the HPT axis. Studies have suggested that omega-3 fatty acids suppress TSH secretion by modulating hypothalamic control over the pituitary gland. Possible mechanisms include reduction in thyrotropin-releasing hormone (TRH) secretion from the hypothalamus, leading to lower TSH release. Alteration of the levels of dopamine and serotonin, both of which regulate TSH secretion. Linseed oil has anti-inflammatory properties, which may reduce inflammation-related HPT axis activation. Chronic inflammation increases TSH, so reducing inflammation may lead to a paradoxical decrease in TSH levels despite low thyroid hormone levels. Type 2 deiodinase (D2) is an enzyme that converts T4 to T3 in the brain and pituitary gland. Linseed oil may inhibit D2 activity, leading to reduced intracellular T3 levels in the pituitary, which paradoxically suppresses TSH release. Omega-3 fatty acids may alter the expression of thyroid hormone transporters in the pituitary, affecting how thyroid hormone regulates TSH. Thus, while linseed oil generally has beneficial effects on metabolism and inflammation, it may suppress TSH production despite lowering T3 and T4 levels through central nervous system modulation, improved thyroid hormone sensitivity, and enzyme regulation (Deshmukh and Patel, 2021).

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Conclusion

Linseed has a preventive effect against Cordarone-induced thyrotoxicity and hepatotoxicity. The omega-3 fatty acids and lignans in linseed may help fight inflammation and oxidation.

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Acknowledgments

We want to thank the head of the animal house at the Pharmacy College, University of Kerbala, and all the other pathologists and chemists who helped us with our work.

Funding

No funding.

Authors’ contributions

All authors suggested the idea for the study, planned it, and implemented it. They also helped prepare the samples, assisted with the statistical analysis of the data, and interpreted the findings. They gave important feedback, helped plan the research, analyze the results, and evaluate the work.

Conflict of interest

The authors state that there are no conflicts of interest to disclose.

Data availability

All data corroborating this investigation’s conclusions are accessible within the publication.

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