Amoxicillin–clavulanic acid induced sperm abnormalities and histopathological changes in mice

Objective To explore the genotoxic potential and histopathological changes induced in liver, kidney, testis, brain and heart after using the antibiotic drug amoxicillin/clavulanic acid (4:1). Methods The study included chromosomal aberration analysis in bone-marrow and mouse spermatocytes, induction of sperm morphological abnormalities and histopathological changes in different body organs. The drug was administrated orally at a dose of 81 mg/kg body weight twice daily (Total = 162 mg/kg/day) for various periods of time equivalent to 625 mg/men (twice daily). Results The results revealed non-significant chromosomal aberrations induced after treatment with amoxicillin/clavulanic acid (AC) in both bone marrow and mouse spermatocytes after 7 and 10 days treatment. On the other hand, statistically significant percentages of sperm morphological abnormalities were recorded. Such percentage reached 8.10 ± 0.55, 9.86 ± 0.63 and 12.12 ± 0.58 at the three time intervals tested (7, 14 and 35 days after the 1st treatment respectively) (treatment performed for 5 successive days) compared with 2.78 ± 0.48 for the control. The results also revealed histopathological changes in different body organs after AC treatment which increased with the prolongation of the period of therapy. Congestion of central vain, liver hemorrhage and hydropic changes in hepatocytes were noticed in the liver. Degenerative changes were found in kidney glomerulus and tubules while testis showed atrophy of seminiferous tubules, and reduction of spermatogenesis. AC also induced neurotoxicity and altered brain neurotransmitter levels. Hemorrhage in the myocardium, disruption of cardiac muscle fibers and pyknotic nuclei in cardiomyocytes were recorded as side effects of AC in heart tissue. Conclusions The results concluded that AC treatment induced sperm morphological abnormalities and histopathological changes in different body organs. Clinicians must be aware of such results while describing the drug.

Mutagenic responses of nickel chloride in somatic and germ cells of mice invitro and invivo studies

The mutagenic response of Nickel chloride [Nicl[2][was evaluated in mice in vitro, in cultured mouse spleen cells. The cytotoxic effect of NiCl[2] was tested, the cultures were treated with the concentrations 10[-3]- 10[-6] M NiCl[2] /ml medium for 24 h The highest percentage of viable cells reached 88.79% in cultures treated with 10[-6] M NiCl[2]/ml medium compared with 92.5% in non-treated cell cultures. NiCl[2] at concentrations 10[-3]-10[-6] M/ml medium induced a significant percentage of chromosomal aberrations. It reached 8.75 +/- 0.65 [P< 0.01] in the cultures treated with 10[-3] M NiCl[2]/ ml medium, after excluding gaps versus 3.25 +/- 0.14 in the non-treated cell cultures. In vivo, single oral treatment by gavage at the doses 5, 25, 50, 75 mg NiCl[2] kg[-1] b. wt. induced an increase in the percentage of chromosomal aberrations in a dose dependent relationship. It's percentage at 75 mg kg[-1] b. wt was 12.2 +/- 1.16[without gaps] in bonemarrow and 10.6 +/- 0.60 [P < 0.01] in spermatocyte cells from that compared with 2.8 +/- .37 and 3.8 +/- 00.37 respectively in non-treated mice [background level]. Repeated treatment with the dose 5 mg NiCl[2] kg[-1] b. wt for 7, 14, 21 and 28 days did not induce a clear increase in the percentage of chromosomal aberrations than the single treatment It reached 8.2 +/- 0.80 [P< 0.05] in bone-marrow cells and 9.0 +/- 0.45 [P < 0.01] in spermatocyte cells after treatment with the dose 5 x 28 [140 mg Nicl[2] kg[-1] b. wt.] The same doses were used to study the morphological sperm- shape abnormalities. The two higher doses of NiCl[2] 50 and 75 mg kg[-1] b. wt induced a dase-dependant and statistically significant [P < 0.05] increase in the percentage of sperm-shape abnormalities. In conclusion, NiCl[2] has a weak mutagenic activity in mice, directly related to its ability to enter the cells. NiCl[2] produces genetic effect in vitro because its delivery and exposure can be controlled, but in vitro water - soluble NiCI[2] is rapidly removed from the body, therefore it induces a low percentage of chromosomal aberrations in somatic and germ cell

protective role of folic acid on the mutagenicity induced by sodium sulfite in different tissues of male mice

The genotoxic effect of sodium sulfite [Na2SO2] one of the oldest food additives was evaluated. Sulfur dioxide [SO2] is liberated in the body after administering Na2SO3 and it is the effective chemical. The induction of chromosome aberrations and sister-chromatid exchange in bone-marrow, chromosome aberrations and sperm abnormalities in germ cells of the mouse was investigated. Oral treatment by gavage with the doses 125, 250 and 625 mg/kg b. wt. [1/20, 1/10 and 1/4 LD50] for 1, 7 and 14 days increased chromosome aberrations in somatic and germ cells in a dose- and time-dependent manner. The same tested doses induced a significant increase in the frequency of SCE's and sperm abnormalities by increasing the dose of treatment. In all experiments mitomycin C induced much higher effect. Administration of folicacid [FA] at a dose of 10 mg/kg b. wt. slightly minimized the genotoxic effect of SO2 in all experiments examined. The results have confirmed that the food additive sodium sulfite is a clastogenic and genotoxic agent and FA is capable of reducing this damage

Genotoxic effect of diethylaminoethanol in mouse bone-marrow and germ cells

The genotoxic potential of the aliphatic amine diethylaminoethanol [DEAE] wasevaluated in vivo using two cytogenetic parameters, chromosomal aberrations inboth somatic and germ cells and sister chromatid exchanges [SCEs]. Theprotective effect of Royal Jelly was also tested. Male Swiss mice weretreated by gavage with DEAE at the dose levels of 100, 150 and 200 mg/kg b.wt. The used doses induced a significant percentage of chromosomalaberrations at 24 hours post-treatment, even after excluding the number ofmetaphases with gaps compared with control. Repeated treatment for three days withthe same dose induced a statistically higher percentage of chromosomalaberrations than single treatment. DEAE induced also a statisticallysignificant percentage of chromosomal aberrations in mouse spermatocytes atdiakinesis metaphase I after single and repeated treatments. The maximumpercentage of the induced aberrations reached 17.06 + 0.95 after repeatedtreatment with the highest tested dose for 3 consecutive days compared with4.8 +/- 0.33 for the controls. DEAE was found to potent inducer of SCEs atthe tested doses 100, 150 and 200 mg/kg b. wt. [P <0.01]. The meanfrequency reached 10.53 +/- 0.38, 12.97 +/- 0.41 and 15.79 +/- 0.52,respectively, compared with 5.54 +/- 0.48 for the controls. Treatment withRoyal Jelly at 1 mg/kg b. wt., decreased the percentage of totalchromosomal aberrations and the frequency of SCEs induced by DEAE in bonemarrow and spermatocyte cells

Induction of chromosome aberrations in mouse germ cells by the organophosphorous insecticides Dursban and Dichlorvos and sperm abnormalities in the treated mice

The ability of the two organophosphorous insecticides "Dursban" and "Dichlorvos" to induce chromosomal abnormalities in mouse spermatocytes was investigated. Male swiss mice were intraperitoneally [i.p] injected with the doses 2, 4, 10 mg/kg[-1] body wt. of "Dursban" [dissolved in 0.1 DMSO] and 2.8, 3.5, 7 mg/kg[-1] body wt. of "Dichlorvos" and samples were taken 6. 24 and 48 hrs after the treatment. The percentage of chromosomal aberrations in diakinesis - metaphase I cells increased by increasing the concentration of both insecticides and reached its maximum 24 hrs following i.p. injection, its highest value was 19.3 +/- 1.61 [P < 0.01] and 16.5 +/- 0.63 [P < 0.01] 24 hrs after treatment with the highest dose of "Dursban" and "Dichlorvos" respectively. Compared with 25.5 +/- 0.97 [P < 0.01], 24 hrs after i.p. injection with mitomycin C" at 1 mg/kg[-1] body wt. The two insecticides induced abnormal chromosomal associations including univalents [autosomal and x-y univalents] and chains, as well as structural and numerical chromosome aberrations. Dursban and Dichlorvos induced a dose-dependent increase in the percentage of abnormal sperm heads. Its highest value was 15.48 +/- 0.73 [P < 0.01] and 10.8 +/- 0.89 [P < 0.01] after oral treatment with Dursban and Dichlorvos respectively, compared with 18.3 +/- 1.10 [P < 0.01] after treatment with "Mitomycin C"

Induction of chromosome aberrations and sister chromatid exchange in mouse bone-marrow by the insecticide dursban

The ability of the insecticide "Dursban" to induce chromosomal aberrations and sister chromatid exchange was tested in mouse bone marrow. Mice were intraperitoneally injected with the dose 4 m kg [-1] body wt. of the insecticide dissolved in 0.1 DMSO. Samples were taken 6, 24 and 48 hours after intraperitoneal injection. The results indicated that "Dursban" at the tested doses is a potent inducer of chromosome aberrations in mouse bone marrow. The percentage of chromosomal aberrations increased by increasing the time of treatment and reached its maximum 24 hours following intraperitoneal injection, where it reached 25.5 +/- 0.95. The aberrations induced were chromatid and chromosome gaps, fragments, breaks and deletions. The doses 10, 20 and 25 mg kg [-1] body wt. of the insecticide caused a significant and dose dependent increase in the frequency of sister chromatid exchange in mouse bone marrow cells. It reached 9.13 +/- 0.27 per cell after treatment with the highest tested does of "Dursban" compared with 4.52 +/- 0.42 per cell in the solvent. This indicates that "Dursban" is a weak inducer of sister chromatid exchange in mouse bone marrow