The ameliorative effects of propolis and/or levothyroxine on propylthiouracil-induced hypothyroidism in adult albino rats

Propolis (PRO), a natural bee product, is known for its anti-inflammatory, antioxidant, and cytoprotective effects. Hypothyroidism, being one of the common endocrine disorders, is considered a state of redox alteration. This study aimed to investigate the ameliorative impact of PRO alone or combined with levothyroxine (LTH) on propylthiouracil (PTU)-induced hypothyroidism. Forty-two male albino rats were randomly assigned to six groups of seven rats each. Group I was designated as the control group (Ctrl), whereas Group II (PRO) received PRO orally by intragastric tube. Group III (PTU) was given PTU via intraperitoneal injection. Groups IV, V, and VI received a combination of PTU with LTH, PRO, or both PRO + LTH, respectively. Following 45 days, serum thyroid hormone levels [triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH)], thyroid levels of antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], oxidative stress marker malondialdehyde (MDA), and inflammatory cytokines [nuclear factor kappa-B (NF-κB) and tumor necrosis factor alpha (TNF-α)] were detected. Histopathological, immunohistochemical, and morphometric assessment of the thyroid gland were performed. Induction of hypothyroidism in the PTU group showed marked functional and architectural alterations, manifested by reduced thyroid hormones T3 and T4, increased TSH levels, as well as depressed SOD, CAT, and elevated MDA levels indicating pronounced oxidative stress. NF-κB and TNF-α levels were notably raised, reflecting the presence of inflammation. This group, as well, exhibited thyroid tissue damage (hypertrophic follicular cells with vacuolated cytoplasm) with increased area fraction % of proliferating cell nuclear antigen (PCNA)-positive cells. Treatment with LTH, PRO, or both PRO + LTH alleviated these effects to varying extents. Strikingly, the combination of both therapies, PRO + LTH, provided the most pronounced protection. It not only reduced the histopathological alterations but also restored the functional parameters to near normal values. These findings highlight the beneficial effect of combining PRO with LTH and its superior impact in hypothyroidism treatment.