Biomedical subjects

S C Srivastava

Publications and source records attributed to S C Srivastava.

At least 19 recordsLinked to original sources

PubMed2000

Marrow-sparing effects of 117mSn(4+)diethylenetriaminepentaacetic acid for radionuclide therapy of bone cancer.

UNLABELLED: Several bone-seeking radionuclides (32P, 89Sr, 186Re, and 153Sm) have been used to treat bone pain. The limiting factor in this modality is marrow toxicity. Our hypothesis is that marrow toxicity can be reduced while maintaining therapeutic efficacy using radionuclides that emit short-range beta particles or conversion electrons (CEs). A recent study on 47 patients using the short-range CE emitter 117mSn(4+)diethylenetriaminepentaacetic acid (117mSn(4+)DTPA) supports this hypothesis. The hypothesis is now tested using 117mSn(4+)DTPA in a mouse femur model. METHODS: The survival of granulocyte-macrophage colony-forming cells (GM-CFCs) in femoral marrow is used as a biologic dosimeter for bone marrow. The dosimeter is calibrated by irradiating mice with exponentially decreasing dose rates of 137Cs gamma-rays with a dose-rate decrease half-time, Td, equal to the effective clearance half-time of 117mSn(4+)DTPA from the femur (222 h). When Td = 222 h, the mean absorbed dose required to achieve a survival fraction of 37% is 151 cGy. After calibration, 117mSn(4+)DTPA is administered and GM-CFC survival is determined as a function of injected activity. These data are used to experimentally determine the mean absorbed dose to the femoral marrow per unit injected activity. The kinetics of radioactivity in the marrow, muscle, and femoral bone are also determined. Finally, a theoretic dosimetry model of the mouse femur is used, and the absorbed doses to the femoral marrow and bone are calculated. RESULTS: The experimental mean absorbed dose to the femoral marrow per unit injected activity of 117mSn(4+)DTPA is 0.043 cGy/kBq. The theoretic mean absorbed dose to the femoral bone per unit injected activity is 1.07 cGy/kBq. If these data are compared with those obtained previously for 32P-orthophosphate, the radiochemical 117mSn(4+)DTPA yields up to an 8-fold therapeutic advantage over the energetic beta emitter 32P. CONCLUSION: The CE emitter 117mSn offers a large dosimetric advantage over energetic beta-particle emitters for alleviating bone pain, and possibly for other therapeutic applications, while minimizing marrow toxicity.

Animals↗

PubMed1999

67Cu-2IT-BAT-Lym-1 pharmacokinetics, radiation dosimetry, toxicity and tumor regression in patients with lymphoma.

UNLABELLED: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced therapeutic responses and prolonged survival in patients with non-Hodgkin's lymphoma when labeled with 1311. Radiometal-labeled antibodies provide higher tumor radiation doses than corresponding 1311 antibodies. 67Cu has an exceptional combination of properties desirable for radioimmunotherapy, including gamma and beta emissions for imaging and therapy, respectively, a biocompatible half-time and absence of pathways contributing to myelotoxicity. The radioimmunoconjugate, 67Cu-21T-BAT-Lym-1, has been shown to be efficacious in nude mice bearing human Burkitt's lymphoma (Raji) xenografts. Based on these results, a clinical study of the pharmacokinetics and dosimetry of 67Cu-21T-BAT-Lym-1 in patients with lymphoma was initiated. METHODS: Eleven patients with advanced stage 3 or 4 lymphoma were given a preload dose of unmodified Lym-1, then an imaging dose of 126-533 MBq (3.4-14.4 mCi) 67Cu-21T-BAT-Lym-1. Total Lym-1 ranged from 25 to 70 mg dependent on the specific activity of the radioimmunoconjugate and was infused at a rate of 0.5-1 mg/min. Imaging, physical examination, including caliper measurement of superficial tumors, and analysis of blood, urine and fecal samples were performed for a period of 6-13 d after infusion to assess pharmacokinetics, radiation dosimetry, toxicity and tumor regression. RESULTS: In 7 patients, in whom superficial tumors had been accurately measured, tumors regressed from 18% to 75% (mean 48%) within several days of 67Cu-21T-BAT-Lym-1 infusion. The uptake and biological half-time of 67Cu-21T-BAT-Lym-1 in tumors were greater than those of normal tissues, except the mean liver half-time exceeded the mean tumor half-time. The mean tumor-to-marrow radiation ratio was 32:1, tumor-to-total body was 24:1 and tumor-to-liver was 1.5:1. Images were of very good quality; tumors and normal organs were readily identified. Mild and transient Lym-1 toxicity occurred in 6 patients; 1 patient developed a human antimouse antibody. There were no significant changes in blood counts or serum chemistries indicative of radiation toxicity. CONCLUSION: Because of the long residence time of 67Cu-21T-BAT-Lym-1 in tumors, high therapeutic ratios were achieved and, remarkably, numerous tumor regressions were observed after imaging doses. The results indicate considerable therapeutic potential for 67Cu-21T-BAT-Lym-1.

Adult↗

PubMed1998

Radionuclide development at BNL for nuclear medicine therapy.

Radionuclides with medium energy beta emission and a several day half-life have often been viewed as attractive candidates for radioimmunotherapy. Among the most promising in this category are 47Sc, 67Cu, 153Sm, 188Re, and 199Au. The production of 67Cu, 153Sm, 199Au at BNL is summarized and the development of the latest candidate for this application, 47Sc, is described in detail. We also summarize the development of another important therapeutic radionuclide, 117mSn for bone pain palliation.

Copper Radioisotopes↗

PubMed1998

Radiochemical purification of no-carrier-added scandium-47 for radioimmunotherapy.

A procedure, adaptable to large-scale remote operation, was developed to purify no-carrier-added (NCA) 47Sc from irradiated Ti targets. Methods based on extraction chromatography and cation-exchange chromatography were compared. Results of this comparison led to the development of an optimized procedure based on cation-exchange with Dowex AG 50W-X4 and 47Sc elution with HCl/HF. This method gave 90-97% overall 47Sc recovery, with a Ti separation factor greater than 2.4 x 10(-5), and specific activities > or = 0.9 GBq microgram-1. Use of the 47Sc product, for labeling monoclonal antibodies, resulted in consistent labeling yields of > or = 90%.

Chromatography, Ion Exchange↗

PubMed1998

In-vivo tissue uptake and retention of Sn-117m(4+)DTPA in a human subject with metastatic bone pain and in normal mice.

Organ and tissue uptake and retention of Sn-117m(4+)DTPA were studied in a human subject treated for metastatic bone pain, and the results were compared with the biodistribution studies in five normal mice. The explanted organs from a patient who received a therapy dose of 18.6 mCi (688.2 MBq) Sn-117m(4+)DTPA and who died 47 days later were imaged with a gamma-camera, and tissue samples were counted and also autoradiographed. Bone, muscle, liver, fat, lungs, kidneys, spleen, heart and pancreas tissue samples were assayed in a well counter for radioactivity. Regions of interest were drawn over bone and major organs to calculate and quantify clearance times using three in vivo Sn-117m(4+)DTPA whole-body scintigrams acquired at 1, 24 and 168 h after injection. Five normal mice injected with the same batch of Sn-117m(4+)DTPA as used for the human subject were sacrificed at 24 h, and tissue samples were collected and assayed for radioactivity for comparison with the human data. For the human subject, whole-body retention at 47 days postinjection was 81% of the injected dose, and the rest (19%) was excreted in urine. Of the whole-body retained activity at 47 days, 82.4% was in bone, 7.8% in the muscle and 1.5% in the liver, and the rest was distributed among other tissues. Gamma-ray scintigrams and electron autoradiographs of coronal slices of the thoracolumbar vertebral body showed heterogeneous metastatic involvement with normal bone between metastatic lesions. There was nonuniform distribution of radioactivity even within a single vertebral body, indicating normal bone between metastatic lesions. Lesion-to-nonlesion ratios ranged from 3 to 5. However, the osteoid-to-marrow cavity deposition ratio, from the microautoradiographs, was 11:1. The peak uptake in the human bone was seen at 137 h with no biological clearance. Soft tissues showed peak uptake at 1 h and exhibited three compartmental clearance components. Whole-body retention in normal mice was 38.7% of the injected dose at 24 h and the rest was excreted. At 24 h postinjection, bone in mice showed 84.2% of the whole-body retention, muscle 1.7% and liver 1.4%, and the rest was distributed in other soft tissues. Percent distribution of the retained dose among bone, muscle, liver and other soft tissues is very similar between mice and a human subject. To calculate precise radiation absorbed doses from bone pain palliation radionuclides, it is necessary to take into account soft-tissue uptake and retention that may not be readily evident from routine external gamma-scintigraphy.

Adenocarcinoma↗

PubMed1998

Treatment of metastatic bone pain with tin-117m Stannic diethylenetriaminepentaacetic acid: a phase I/II clinical study.

The physical characteristics of Sn-117m combined with the biodistribution of the compound tin-117m (Stannic, 4+) diethylenetriaminepentaacetic acid (Sn-117m DTPA) suggest that it should be an excellent agent for the palliation of pain from bony metastases. Prior work has established the dosimetry and the safety for the material in human beings. The presence of low-energy conversion electrons should result in the relative sparing of the bone marrow while delivering a high radiation dose to sites of bony metastatic disease. Forty-seven patients with painful bone metastases from various malignancies were treated with Sn-117m DTPA. The patients were assigned to five different dose levels ranging from 2.64 to 10.58 MBq (71-286 microCi) per kg of body weight. Follow-up included review of pain diaries, performance scores, analgesic requirements, blood chemistries, and hematological assessment. Three patients received a second treatment. There was an overall response rate for relief of pain of 75% (range, 60-83%) in the 40 treatments that could be evaluated. No correlation was apparent in this limited series between response rate and the five dose levels used. The relief was complete in 12 patients (30%). The time to onset of pain relief was 19 +/- 15 days with doses < or = 5.29 MBq/kg and 5 +/- 3 days with doses > or = 6.61 MBq/kg. Myelotoxicity was minimal, with only one patient having a marginal grade 3 WBC toxicity. On the basis of our data, Sn-117m DTPA should be an effective and safe radiopharmaceutical for palliation of painful bony metastases. A large-scale trial is warranted to evaluate it in comparison to other similar agents.

Bone Marrow↗

PubMed1998

Radiopharmaceuticals for bone malignancy therapy.

OBJECTIVE: This continuing education article reviews radionuclide bone therapy agents that are available commercially and introduces agents that are being evaluated for future use. Currently these agents are used to provide pain palliation from metastases to bone. Future applications may include adjuvant therapy to surgery or external beam treatment. After reading this paper, the reader should be able to: (a) describe the desirable characteristics of radionuclide bone therapy agents; (b) compare and contrast radiopharmaceuticals available for bone therapy; and (c) state the clinical applications of radionuclide bone therapy agents.

Bone Marrow↗

PubMed1997

Enhancement of 67Cu-2IT-BAT-LYM-1 therapy in mice with human Burkitt's lymphoma (Raji) using interleukin-2.

BACKGROUND: Lymphomas have been shown to be responsive to 131I immunoconjugates in studies conducted in mice and patients. We have observed that copper 67 (67Cu)-labeled Lym-1 remains in lymphomatous tissue longer than 131I-Lym-1 and, consequently, results in higher absorbed radiation doses to tumors. In addition, recombinant interleukin-2 (rIL-2) has been reported to increase tumor uptake of radiolabeled antibody. Therefore, we examined the efficacy of 67Cu-labeled Lym-1 and the ability of rIL-2 to enhance this efficacy in athymic mice implanted with Raji xenografts. METHODS: 6[p-(bromoacetamido) benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N', N'',N'''-tetraacetic acid (BAT) was conjugated to Lym-1 via 2-iminothiolane (2IT) to prepare 2IT-BAT-Lym-1, which was labeled with 67Cu. Mice with Raji xenografts were treated with 335-500 microCi (12.4-18.0 MBq) of 67Cu-2IT-BAT-Lym-1 with or without 48,000-144,000 IU of rIL-2 once or were treated b.i.d. for 5 days beginning simultaneously with 67Cu-2IT-BAT-Lym-1. Mouse weight, blood counts, and mortality were monitored to assess toxicity, and tumor size was measured to assess efficacy. In addition, groups of mice were sacrificed to assess the biodistribution of 67Cu-2IT-BAT-Lym-1 with and without rIL-2. RESULTS: In mice treated with 335 microCi of 67Cu-2IT-BAT-Lym-1 alone, 28% of tumors were cured. When 48,000 IU of rIL-2 were added, 50% were cured. The overall response-rate was 50% for both regimens. In mice treated with 400 microCi of 67Cu-2IT-BAT-Lym-1 alone, 42% responded, all of which were cured. When 48,000 IU of rIL-2 were added, 77% of tumors responded, and 38% were cured. Larger or multiple doses of rIL-2 did not result in additional therapeutic enhancement. The tumor uptake and radiation dose after 67Cu-2IT-BAT-Lym-1 were about two times greater when a single dose of rIL-2 was added: This may be the basis for enhanced therapeutic efficacy. Mortality was not altered for 335 microCi or 400 microCi doses of 67Cu-2IT-BAT-Lym-1 by rIL-2 nor were other toxicity parameters. Mortality was increased at 500 microCi by the addition of rIL-2. CONCLUSIONS: 67Cu-2IT-BAT-Lym-1 provided a therapeutic and frequently curative dose of radiation to tumored mice at tolerated doses. The therapeutic effectiveness of 67Cu-2IT-BAT-Lym-1 may have been enhanced by rIL-2.

Animals↗

PubMed1997

Tin-117m(4+)DTPA: pharmacokinetics and imaging characteristics in patients with metastatic bone pain.

UNLABELLED: Biokinetics and imaging characteristics of 117mSn(4+)DTPA have been studied in patients with metastatic bone pain. METHODS: Seventeen patients with bone pain due to metastasis were given three dose levels: 180 microCi/kg (6.66 MBq/kg), 229 microCi/kg (8.47 MBq/kg) and 285 microCi/kg (10.55 MBq/kg) body weight. Periodic blood and daily urine samples were collected for 14 days to measure percent injected activity retained in blood and that excreted in urine. Simultaneous anterior and posterior view whole-body images were obtained under identical scan settings at 1, 3.5 and 24 hr and on Days 3 and 7 and between 4-6 and 8-10 wk postinjection. The total body retention was calculated using the geometric mean counts. RESULTS: After intravenous injection, the total body clearance of 117mSn(4+)DTPA shows two components: a soft-tissue component and a bone component. The soft-tissue component accounts for 22.4% of the dose and consists of four subcomponents with an average biologic clearance half-time of 1.45 days (range 0.1-3.2 days). The bone component accounting for the remaining 77.6% of the dose shows no biologic clearance. A mean 22.4% of the dose is excreted in urine in 14 days; 11.4% within 24 hr. The uptake pattern appears similar to that of 99mTc-MDP. Peak uptake is observed in normal bone by 24 hr and metastatic lesions by 3-7 days. Pain palliation was observed with all three doses levels. CONCLUSION: Among the four potential bone pain palliation radionuclides, 117mSn(4+)DTPA demonstrates the highest bone uptake and retention. Some biokinetic and radionuclidic features of 117mSn(4+)DTPA are similar to other agents, but many features are different and unique and may make it an ideal bone pain palliation agent. Double-blind comparative studies are needed to determine its exact role in bone pain palliation.

Adult↗

PubMed1997

Efficacy and toxicity of 67Cu-2IT-BAT-Lym-1 radioimmunoconjugate in mice implanted with human Burkitt's lymphoma (Raji).

Radioimmunotherapy has shown promising results for treatment of radiosensitive malignancies such as lymphoma. Positive responses have been reported in patients with non-Hodgkin's lymphoma treated with 131I-radiolabeled Lym-1, a mouse anti-lymphoma monoclonal antibody. In this study, the efficacy of 67Cu-radiolabeled Lym-1 was examined. Nude mice bearing human Burkitt's lymphoma (Raji) tumors (20-524 mm3) were treated with 12.4, 14.8, 18.5, and 23.3 MBq of 67Cu-2IT-BAT-Lym-1. Tumor size was measured to assess efficacy, and mouse weight, blood counts, and mortality were monitored to assess toxicity. In mice treated with 12.4, 14.8, and 18.5 MBq of 67Cu-2IT-BAT-Lym-1, 50% (9 of 18), 42% (5 of 12), and 50% (3 of 6) of tumors achieved remission or cure; 33% of tumors were cured overall; and significant regrowth delay was observed. The 23.3 MBq dose group did not yield meaningful efficacy data because of high mortality. In control groups receiving 14.8 and 18.5 MBq of the isotype-matched nonspecific monoclonal antibody radioimmunoconjugate, 67Cu-2IT-BAT-L6, 0% (0 of 15) and 17% (2 of 12) of tumors achieved a response; hence, targeted delivery of radiation was the dominant antitumor mechanism of 67Cu-2IT-BAT-Lym-1. LD50/30 for mice treated with 67Cu-2IT-BAT-Lym-1 and -L6 were 21.6 and 20.6 MBq, respectively. In conclusion, 67Cu-2IT-BAT-Lym-1 provided a therapeutic and frequently curative dose of radiation to tumored mice with modest toxicity.

Animals↗

PubMed1996

Is there life after technetium: what is the potential for developing new broad-based radionuclides?

The use of radionuclides for medical and for a multitude of other basic research applications has continued to grow at a very rapid pace. Procedures, based on their use as radiotracers for nuclear medicine imaging and for radiotherapy of cancer and other pathology, have become firmly established as important clinical modalities. It is estimated that on an annual basis in the United States alone, radionuclides are used medically in over 13 million imaging procedures, in over 100 million laboratory tests, and in an ever increasing number (> 100,000) for therapeutic administrations. One out of every four hospital patients undergoes a procedure that involves the use of radionuclides. Diagnostic imaging methods using planar/single-photon emission computed tomography and positron-emission tomography (PET) imaging, as well as the measurement of in vivo organ function, physiology, or biochemistry, have become indispensable tools in patient workup and management. More than 80% of all imaging studies (mostly anatomic) currently use technetium-99m (99mTc), because it has turned out to be the ideal isotope from various considerations. However, over the past few years, nuclear medicine has experienced a slow but steady evolution towards functional studies, quantitative PET imaging, and novel therapeutic approaches. New radionuclides are required for these applications, and their development has attracted considerable interest. This article reviews the current status and future prospects for the development of many new potential isotopes. Practical issues, such as the feasibility of large-scale production and wide-spread availability in a continuous reliable fashion, are addressed. To date, the data are not sufficient to answer the question as to whether any of these radionuclides (or their applications, for that matter) will eventually assume as broad-based a role as that of 99mTc. Nonetheless, there are a number of promising radionuclides that could assume an important place in the future practice of nuclear medicine.

Gamma Rays↗

PubMed1996

Criteria for the selection of radionuclides for targeting nuclear antigens for cancer radioimmunotherapy.

The potential of utilizing immunoconjugates to selectively deliver radionuclides for the destruction of tumors has stimulated much research activity. From dosimetric and other considerations, the choice of radiolabel is an important factor that needs to be optimized for maximum effectiveness of radioimmunotherapy (RIT). This paper reviews and assesses a number of present and future radionuclides that are particularly suitable for RIT based on the various physical, chemical, and biological considerations. Although intermediate to high-energy beta emitters (with and without gamma photons in their emission) possess a number of advantages for most RIT, the use of alpha, Auger, and short range conversion electron emitters could be attractive for targeting nuclear antigens when the radioimmunoconjugate is internalized into tumor cells. Factors relating to the production and availability of candidate radionuclides as well as their stable chemical attachment to monoclonal antibodies are discussed.

Antigens, Nuclear↗

PubMed1996

Pre-clinical and clinical studies of two new bifunctional chelating agents for immunoscintigraphy with 111In-anti-CEA monoclonal antibody.

Anti-CEA F(ab')2 monoclonal antibody fragments [F6 MAb F(ab')2] were conjugated to two bifunctional semi-rigid chelating agents derived from trans-1,2-diaminocyclohexane tetraacetic acid (CDTA), the monolithium salt of N-[methyl(2-isothiocyanatoethyl)carbamide] trans-1,2-diaminocyclohexane-N,N',N'-triacetic acid (SCN), and 4 isothiocyanato-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (4-ICE) and labelled with 111In to obtain IIIIn-labelled-F6 MAb F(ab')2 conjugates (111In-F6-SCN and 111In-F6-4-ICE respectively). Biodistribution in mice and clinical studies were undertaken to assess the potential of these two ligands in the detection of colorectal adenocarcinoma recurrences and metastases in humans. Toxicity studies were carried out on guinea pigs and Swiss mice injected with a dose proportionally 100 times greater than that used in human studies. Clinical studies were performed in patients with clinically and/or biologically suspected adenocarcinoma recurrences. No immunoconjugate-induced toxicity was found. The biodistribution studies in mice gave better visualization of tumour sites with 111In-F6-SCN and 111In-F6-4-ICE than with 111In-F6-DTPA. Ten patients were included in the clinical protocol. 111In-F6-SCN and 111In-F6-4-ICE effectively visualized adenocarcinoma recurrences. However, in this small series, 111In-F6-4-ICE performed somewhat better than 111In-F6-SCN. The present study has demonstrated the potential of new bifunctional semi-rigid chelating agents coupled to antibody and labelled with 111In to localize recurrences (especially in liver) in humans using a one-step targeting method.

Adenocarcinoma↗

PubMed1996

Radiolabeled bone-seeking radiopharmaceuticals.

Bone seeking radiopharmaceuticals consist of diagnostic (primarily single photon emitters) and therapeutic agents. The therapeutic radiopharmaceuticals are utilized on the basis of their particulate emissions (primarily beta-) and thus are treated differently than the single photon bone imaging agents. Lately, the therapeutic bone seekers have attained increasing importance due to their potential role in alleviating pain from osseous metastases in cancer patients. However, there seems to be a paucity of published data on the pharmacokinetics of most of these agents. This paper will briefly review and summarize the presently available pharmacokinetic information on the various therapeutic bone seeking radiopharmaceuticals. Bone imaging agents based on single photon emitters will not be covered since they have been extensively discussed in the published literature.

Animals↗

PubMed1995

Factors regulating methyl mercury uptake in a cyanobacterium.

The simultaneous addition of dithiothreitol (DTT), mercaptoethanol, and glutathione (30 microM each) and CH3Hg+ to Nostoc calcicola cells reduced CH3Hg+ uptake in the order GSH > DTT > mercaptoethanol. However, the preexposure of cyanobacterial cells to similar thiols resulted in different pattern of CH3Hg+ uptake in the sequence: GSH > mercaptoethanol > DTT. Light-grown cyanobacterial cells demonstrated a faster initial uptake of CH3Hg+ (rate 0.619 mumol CH3Hg+ mg-1 protein min-1, 10 min) with a biphasic pattern saturating at 30 min (bioconcentration factor = 2.7 x 10(3)). 3-(3,4-Dichlorophenyl)-1,1'-dimethyl urea (30 microM) reduced the uptake rate by 5% with a corresponding 33% reduction in CH3Hg+ accumulation. Dark exposure (24 hr) of cells reduced the CH3Hg+ uptake rate (22.3%) accompanied by a considerable decline in the bioconcentration factor (1.4 x 10(3)). Of the four permeabilizers used, p-chloromercuribenzoate (1 microM) proved most effective in altering the CH3Hg+ uptake kinetics while dimethyl sulfoxide (5%) and cetyl trimethylammonium bromide (1%) lowered the bioconcentration factor to 2.2 x 10(3) and 1.2 x 10(3), respectively. After toluene exposure, however, the cells revealed no sign of CH3Hg+ uptake. The data have been discussed in light of the role(s) of thiols, photoautotrophy, and membrane integrity in regulating the cellular influx of CH3Hg+.

Cyanobacteria↗

PubMed1995

Effect of hexachlorocyclohexane (HCH) on testicular plasma membrane of rat.

The study deals with the analysis of residue of hexachlorocyclohexane (HCH) and its possible damaging potential on testicular plasma membrane of rats. In vitro studies were conducted by exposing plasma membrane of testis with 1.46 x 10(-5) M, 2.92 x 10(-5) M, 4.38 x 10(-5) M, 7.30 x 10(-5) M, 1.46 x 10(-4) M and 2.92 x 10(-4) M HCH at 37 degrees C for 15 min. The results indicate inhibition in the activity of the Ca(2+)-ATPase, Na(+)+K(+)+Mg(2+)-ATPase and 5'Nucleotidase. In vivo studies were carried out following repeated dermal exposure to HCH at a dose level of 50 or 100 mg/kg/day for 60 days to male rats. The results show significant decrease in the activities of 5'-Nucleotidase, Ca(2+)-ATPase, Na(+) + K(+)-ATPase and Mg(2+)-ATPase in the plasma membrane of testis following exposure to HCH. The analysis of the residues of HCH reveals the presence of significant quantities of its different isomers viz., alpha, beta, gamma and delta in the testicular plasma membrane of rats given in vivo dermal exposure of this pesticide. These results suggest that the presence of HCH residue may be a factor in inhibiting the marker enzymes of the plasma membrane of testis.

5'-Nucleotidase↗

PubMed1995

Effect of dermal application of hexachlorocyclohexane (HCH) on male reproductive system of rat.

1. The toxic manifestations of dermally applied hexachlorocyclohexane (50 mg or 100 mg kg-1 body weight day-1, 5 days in a week for 120 days) on testes and sperm of rat have been investigated. 2. The results indicate that exposure of HCH through the dermal route could lead to an alteration in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH), gamma-glutamyl transpeptidase (gamma-GT) and beta-glucuronidase (beta Gluc.) associated with specific cell types. 3. Significant quantities of HCH and its isomers accumulated in testes as well as sperm of treated rats. 4. HCH exposure also led to a decrease in serum testosterone levels, epididymal sperm count, sperm motility and an increase in the percentage of abnormal sperm. 5. These observations indicate the possibility of adverse effects of HCH on the male reproductive functions of men exposed dermally to this pesticide in industry or during spraying in the field.

Administration, Topical↗

PubMed1995

Effect of oral administration of carbofuran on male reproductive system of rat.

1. Carbofuran was administered orally to adult male rats at dose levels of 0.1, 0.2, 0.4 or 0.8 mg kg-1 body weight, 5 d wk-1 for 60 days. A dose dependent decrease was observed in body weight of rats treated with 0.2-0.8 mg carbofuran kg-1 body weight. 2. A significant decrease in the weight of epididymides, seminal vesicles, ventral prostate and coagulating glands was observed at various test doses of carbofuran except at the lowest dose. 3. Decreased sperm motility, reduced epididymal sperm count along with increased morphological abnormalities in head, neck and tail regions of spermatozoa were observed in rats exposed to 0.2, 0.4, or 0.8 mg carbofuran kg-1 body weight. 4. In addition, significant alterations were observed in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH) (decreased), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (gamma-GT) (increased) depending on dose. 5. Histologically, the results indicated the toxicity of carbofuran on testes depending on dose. The changes predominantly consisted of moderate oedema, congestion, damage to Sertoli cells and germ cells, along with the accumulation of cellular debris and presence of giant cells in the lumen of a few seminiferous tubules which showed disturbed spermatogenesis with the higher doses of carbofuran. 6. These observations determined a no effect level dose of 0.1 mg kg-1 body weight of carbofuran on the biochemical and morphological indices studied for male reproductive toxicity assessment in the rat model. The results of the present study provide first hand information on the reproductive toxicity of carbofuran in male rats.

Administration, Oral↗