Profiles 2016

Salah Sumar Al Zadjali

Department of Pharmacology

College of Medicine and Health Sciences

Dissertation

Title

Experimental Investigation on the Relationship between Lead Exposure, Thyroids and Systemic

Toxicity in Health and Diabetes

Faculty Advisor

Dr. Abdu Adem

Defense Date

26 April 2015

Abstract

Lead exposure can cause multiple systemic toxicities, particularly affecting the hematopoietic, nervous and renal systems.

However, its effects on the thyroid functions are not well elucidated and the pub-lished studies are controversial. In addition,

although there are several experimental thyroid models, each one of them has its own limitations. Accordingly, in this

dissertation, we investigated the possible rela-tionship between lead exposure, thyroid functions and short-term systemic

toxicity in two animal mod-els, namely normal (non-diabetic) and diabetic animals. We also investigated the possibility of

develop-ing a hormonal thyroid model. In the non-daibetic model, Wistar rats were divided into five groups and treated

for five days. The four treatment groups received 1, 25, 50, or 100 mg/ kg of lead acetate trihy-drate intraperitoneally

(i.p.), respectively. The control group received i.p. injections of distilled water. As for the diabetic model, diabetes was

induced with an i.p. injection of 60 mg/ kg streptozocin (STZ). Six weeks later, lead exposure experiments started. Here, four

groups were studied i.e. a control; and 25, 50 and 100 mg/ kg lead acetate groups. In each model, the measured blood

lead levels correlated very well with the administered doses of lead acetate. Treatment of the animals with lead acetate

resulted in signif-icant weight loss in both models. Lead exposure caused a dose-related increase in thyroid stimulating

hormone (TSH) in non-diabetic and diabetic animals. Although, thyroxine (T4) and triiodothyronine (T3) levels remained

within normal range in non-diabetic animals, their levels were reduced in diabetic ani-mals. The highest dose of lead (100

mg/ kg) significantly increased white blood cell counts and caused a significant decrease in the number of platelets in

non-diabetic animals. In addition, C-reactive protein levels increased significantly in response to lead exposure in this

model. Moreover, there was a signifi-cant increase in lactate dehydrogenase (LDH), aspartate aminotransferase, total

bilirubin, and urea levels; following lead exposure in non-diabetic animals. On the other hand, lead exposure in diabetic

animals increased urea levels and caused a significant decrease in creatinine levels in plasma. While the concen-trations

of malondialdehyde were not affected, glutathione stores were depleted in response to lead exposure in the diabetic

the last stage, we tried to develop a new experimental thyroid model, based on the use of hormones. In this

regard, animals were treated for five days with either thyrotropin-releasing hormone (TRH) or octreotide (OCT) to induce

hyperthyroidism or hypothyroidism, respectively. Although there were no effects on T4 and T3 levels, TRH was effective

in causing an increase in TSH levels. However, TRH also elevated LDH levels. The use of TRH did not cause any other

side effects on the tested parameters, which included weight change, oxidative stress markers and renal and hepatic

functions. In comparison, OCT failed to affect TSH, T4 and T3 levels, at the dose and treatment duration that we used. In

conclusion, short-term lead exposure in healthy and diabetic animal models affected the functions of the anterior pituitary

and thyroid glands, caused oxidative stress, liver and kidneys toxicity and induced systemic inflammation. In addition, we

found that TRH has a potential to induce hyperthyroidism in experimental animals. Keywords: lead; rat; diabetes; thyroid;

experimental model and systemic toxicity.