Toxicological effects of thimerosal on rat kidney: a histological and biochemical study / Efeitos toxicológicos do timerosal no rim de rato: um estudo histológico e bioquímico

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study

Abstract Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-B), tumor necrosis factor- (TNF-), Interleukin-1 (IL-1), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

Resumo O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-B), fator de necrose tumoral- (TNF-), interleucina-1 (IL-1), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study.

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

Development and characterization of novel cell lines from Etroplus suratensis and their applications in virology, toxicology and gene expression.

Four novel cell lines from tissues of eye, gill, kidney and brain of Etroplus suratensis were developed and characterized. The cell lines of eye, gill, kidney and brain were sub-cultured for 245, 185, 170 and 90 passages, respectively, since 2008. These cell lines showed predominantly epithelial-like cells. Effects of temperature and foetal bovine serum concentration on the growth of these cell lines were examined and optimum growth was found at the temperature of 28° C with 20% foetal bovine serum. All the four cell lines were successfully cryopreserved and revived at different passage levels. Cell-cycle analysis of these cell lines was carried out by fluorescence-activated cell sorting. Polymerase chain reaction (PCR) products obtained from the cells and tissues of E. suratensis with primers specific to the conserved region of 16S ribosomal RNA and cytochrome oxidase I genes of E. suratensis revealed the origin of cell lines from E. suratensis. Antibodies raised against the tissues and cells of eye, kidney and gill were highly cross reacted to their specific tissue and cells of E. suratensis. Chromosomal analysis revealed that E. suratensis cells have a normal diploid karyotype with 2n = 48. The cells of these cell lines were successfully transfected with pEGFP vector DNA. The eye (IEE), gill (IEG) and kidney (IEK) cell lines were found to be susceptible to nodavirus but resistant to infectious pancreatic necrosis virus (IPNV). The cells of gill, kidney and eye were applied to test the cytotoxicity of tannery effluents.

Xeroderma pigmentosum with adult Wilms' tumour. A rare association.

Xeroderma pigmentosum is an uncommon skin disorder associated with increased incidence of skin tumours and, less often, internal malignancies. Wilms' tumour is a common paediatric tumour, observed rarely in adults. Here we report the rare association of Xeroderma pigmentosum with adult Wilms' tumour in two Libyan females. To the best of our knowledge, this association has not been reported so far in the literature.

Malakoplakia of the prostate gland--report of two cases and review of the literature.

Malokoplakia of the prostate is extremely rare. We report two cases of prostatic malokoplakia in one 60-year-old and one 64-year-old Libyan man, who both were presented with enlarged prostate containing firm to hard nodules. These cases may be misdiagnosed as carcinoma clinically, but the histology points out the correct diagnosis with the presence of Michaelis-Gutmann bodies in the proliferating histiocytes.

Knowledge, attitude and practice survey of acquired immune deficiency syndrome (AIDS) among paramedicals in a tertiary care hospital in Pakistan.

A knowledge, attitude and practice survey of acquired Immune Deficiency Syndrome (AIDS) was conducted among 805 paramedics at a tertiary care hospital in Islamabad in mid 1993. The mean age of the study population was 29.0 +/- 7.2 years and 59% were males. Almost 25% individuals either had no or upto primary level education. Initial response of 10% subjects was not having heard of AIDS and 70% thought their knowledge was sketchy, while 43% could not mention any cause for the disease. Almost 50% did not know that HIV infection could be asymptomatic. With respect to attitudes about AIDS, 30% subjects thought that changing life style shall have no effect on avoiding AIDS, 50% were of the view that at present AIDS did not pose a significant threat to them and 4% individuals however, admitted to having risk of contracting the disease. There existed significant gaps in the knowledge and attitudes of paramedical staff about AIDS and correlated with the level of education of the staff. These deficiencies need to be addressed through developing health education packages in local languages, targeted especially towards paramedical staff.

Neurologic deficits in major pelvic injuries.

Nerve injury is a common complication of major pelvic injuries. Of 73 patients examined who suffered major pelvic injuries, 24 (33%) had resultant neurologic deficits. The extent of nerve injury is proportionate to the severity of the posterior pelvic bone injury. Sacroiliac dislocation and sacral fractures may be equally complicated by nerve injury. This study suggests that nerve recovery starts three months after injury and stops after two years. Complete recovery was not recorded in severe nerve injuries. Eighty percent of patients recovered from impotence. Nerve injury was found to affect the functional outcome of patients with pelvic injuries. For these reasons, injury should be considered and looked for in every case of pelvic injury.

Brucella arthritis: a study of 96 cases in Kuwait.

Of 400 patients with brucellosis, 104 (26%) had arthritis, of whom 96 could be followed up. The systemic disease in the 96 patients was acute in 54 (56%), subacute in 24 (25%), and chronic in 18 (19%). The main presenting symptoms were joint pain, fever, sweating, and easy fatigability. The joints most commonly affected were the sacroiliac joint (26%) and knee (25%) followed by hip (18%) and spine (8%). There was no particular pattern of joint affection in relation to age. Joint effusion occurred in 32/104 (30%) of cases, predominantly (94%) in the acute group. Culture of synovial fluid was negative in all, and analysis of synovial fluid for cellular profile, glucose, and protein content was not particularly helpful in diagnosis. Plain radiographs did not show major pathological changes. Among the laboratory tests, including haematological and liver function tests, the brucella enzyme linked immunosorbent assay (ELISA) was the most reliable in the diagnosis of disease, using serum and synovial fluid specimens. Treatment with a combination of streptomycin plus tetracyclines or rifampicin resulted in an excellent cure rate and resolution of arthritis without sequelae or mortality. Thus brucellosis should be considered in the differential diagnosis of arthritis, especially in areas in which the disease is endemic.

External fixation of the injured pelvis. The functional outcome.

External fixation was used in 42 patients as the sole definitive treatment for their unstable pelvic fractures. At an average follow-up of 40 months, the anatomical outcome was related to the functional outcome using defined criteria. The functional results were better than the anatomical results. Function improved during the first 18 months and thereafter was stable. The stab and percutaneous techniques for pin insertion had lower rates of infection than the incisional technique. External fixation has a definite role in the treatment of unstable pelvic fractures. In contrast to internal fixation, this method has two major advantages: safety and simplicity.

Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis in three related children and the association with Sweet syndrome in two siblings.

Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis, uncommon childhood diseases of unknown cause, occurred in three children (two brothers and a female cousin). Their parents are consanguineous, and the clinical course of their illness was similar. The two brothers also had Sweet syndrome. The association of Sweet syndrome with chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia in this family suggests that these rare conditions may be interrelated.

Grading the outcome of pelvic fractures.

A system for assessment of function after major pelvic injuries is proposed. This numerical system developed from a five-year prospective study of 60 patients. Five factors were assessed and scored: pain, standing, sitting, sexual intercourse and work performance. The total score then gave a clinical grade as excellent, good, fair or poor. The scoring system allows comparison between early and late results and also between various methods of treatment.

Incisional hernia through iliac crest defects. A report of three cases with a review of the literature.

Although the iliac crest is the most common site from which autogenous bone grafts are obtained, complications are surprisingly rare. One of these is incisional hernia through the resulting bony defect. Occasionally, the herniated contents may proceed to obstruction or strangulation and require emergency surgery. Elective repair of such hernias is advisable in order to avoid such complications. Attention to primary closure of bony iliac defects when complete is mandatory to prevent the occurrence of incisional hernia.

Internal fixation of ipsilateral trochanteric and femoral shaft fractures by staples and Kuntscher nail.

Ipsilateral trochanteric and femoral shaft fractures are rare. A 72-year-old man with such fractures was successfully treated with staples and a Kuntscher nail. The technique was simple and the mechanical stabilization secure. This method is suggested for stable ipsilateral trochanteric and femoral shaft fractures.