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.

Prevention of renal dysfunction by nutraceuticals prepared from oil rich plant foods

<p><b>OBJECTIVE</b>To investigate the protective effect of extracts prepared from avocado, walnut, flaxseed and Eruca sativa seeds in a rat model of kidney dysfunction induced by intraperitoneal cisplatin.</p><p><b>METHODS</b>Ethanol and petroleum ether extracts mixture was prepared from each plant. Six groups of rats were conducted; control healthy, cisplatin group and four test groups where rats were given daily oral dose of each extract mixture before cisplatin injection. Different biochemical and cytogenetic parameters and kidney histopathology were determined. Acute toxicity was tested for the nutraceuticals. Total phenolic contents, fatty acids (FA) and unsaponifiable matter were assessed in the extracts.</p><p><b>RESULTS</b>Walnut ethanol extract showed the highest content of total phenolic. FA analysis revealed that all the studied plants were rich in unsaturated FA. Gas-liquid chromatographic investigation of the unsaponifiable matter showed the presence of campesterol, stigmasterol and β-sitosterol in all the studied plants. Cisplatin treatment induced significant increase in plasma urea, creatinine and malondialdehyde along with significant reduction of plasma albumin, total protein, catalase and total antioxidant as well as reduction in creatinine clearance. Histopathological examination proved the induction of kidney dysfunction. Some sorts of chromosomal aberration and sperm-shape abnormalities were noticed after cisplatin treatment. Administration of extracts mixtures produced improvements in biochemical, histopathological and cytogenetic parameters.</p><p><b>CONCLUSIONS</b>Administration of the studied nutraceuticals proved to possess protective role against cisplatin-induced nephrotoxicity, chromosomal aberration and abnormal sperms. All studied nutraceuticals showed complete safety.</p>

Prevention of renal dysfunction by nutraceuticals prepared from oil rich plant foods

Objective: To investigate the protective effect of extracts prepared from avocado, walnut, flaxseed and Eruca sativa seeds in a rat model of kidney dysfunction induced by intraperitoneal cisplatin. Methods: Ethanol and petroleum ether extracts mixture was prepared from each plant. Six groups of rats were conducted; control healthy, cisplatin group and four test groups where rats were given daily oral dose of each extract mixture before cisplatin injection. Different biochemical and cytogenetic parameters and kidney histopathology were determined. Acute toxicity was tested for the nutraceuticals. Total phenolic contents, fatty acids (FA) and unsaponifiable matter were assessed in the extracts. Results: Walnut ethanol extract showed the highest content of total phenolic. FA analysis revealed that all the studied plants were rich in unsaturated FA. Gas-liquid chromatographic investigation of the unsaponifiable matter showed the presence of campesterol, stigmasterol and β-sitosterol in all the studied plants. Cisplatin treatment induced significant increase in plasma urea, creatinine and malondialdehyde along with significant reduction of plasma albumin, total protein, catalase and total antioxidant as well as reduction in creatinine clearance. Histopathological examination proved the induction of kidney dysfunction. Some sorts of chromosomal aberration and sperm-shape abnormalities were noticed after cisplatin treatment. Administration of extracts mixtures produced improvements in biochemical, histopathological and cytogenetic parameters. Conclusions: Administration of the studied nutraceuticals proved to possess protective role against cisplatin-induced nephrotoxicity, chromosomal aberration and abnormal sperms. All studied nutraceuticals showed complete safety.

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 effects of vitamin c, folic acid and vitamin B12 on the mutagenic effect of methotrexate

In this study, methotrexate [MTX], a widely used anticancer drug, was tested for its potential mutagenicity in mice. An in vivo assay using two cytogenetic parameters, sister chromatid exchanges [SCEs] and chromosome aberrations [CA] in both somatic and germ cells, was done. Also, the possible protection provided by the natural antioxidant ascorbic acid [vitamin C, VC] as well as the possible scavenging properties of pteroylglutamic acid, folic acid [FA] and cyanocobalamin [vitamin B12, VB12] against the mutagenic effect of MTX were assessed. Single intraperitoneal [i.p.] treatment using 2, 5, 10, 20 mg MTX kg-1 b. wt. showed that MTX is a potent inducer of SCEs which induced a dose-dependent increase in the frequency of SCEs. The same tested doses induced an increased percentage of CA in mouse bone marrow as well as in the primary spermatocyte cells in a dose- dependent relationship. Such percentage was statistically highly significant with the two higher doses. This induction was enhanced by multiple treatments with the drug at a dose level of 10 mg kg-1 b. wt. for 4 consecutive days. For studying the possible protective effect, the mice were orally treated by gavage with VC at 50 mg kg-1 b. wt., FA at 25 mg kg-1 b. wt. and VB12 at 0.3 mg kg-1 b. wt., concurrent administration plus the repeated dose of MTX. The results revealed that CA induced with MTX was reduced to a significant extent when the treated mice received FA or VB12 but not with VC

Monosodium glutamate genotoxicity in mice

The genotoxic effect of monosodium glutamate [MSG] was investigated usingdifferent cytogenetic parameters. Different dose levels were studied rangingfrom 0.8 g/kg b. wt. [amount typically added to food] to 1.6, 3.2 g/kg b.wt. Single intraperitoneal treatment with MSG at the tested concentrationshad no effect with respect to the induction of sister chromatid exchanges[SCEs] in mouse bone-marrow cells. The same doses showed normal percentage of micronucleated polychromatic erythrocytes [PEs] after oral treatment bygavage for seven consecutive days. Marrow toxicity was not observed as indicatedby normal percentage of PEs as compared with that in the untreated mice. With respect to chromosomal aberrations in bone marrow cells, gaps were foundto be the most sensitive type of aberrations induced after oral treatment[gavage and feeding] with the different concentrations of MSG. The percentageof the induced aberrations was found to be nonsignificant after excluding thenumber of metaphases with chromatid and chromosome gaps as compared with thenegative control. In germ cells oral treatment by gavage at the doses of 1.6,3.2 g/kg b. wt. MSG induced significant percentage of chromosomalaberrations [P <0.05] in 1ry spermatocytes after 2 and 3 weeks as comparedwith the negative control. The same result was observed in groups of mice fed0.8 g MSG/kg1 b. wt. 1/day mixed with the diet for 2 and 3 months. Thedoses 1.6, 3.2 g/kg b. wt. MSG induced also significant percentage ofabnormal sperms. Such percentage reached 4.12 +/- 0.1 [P <0.05] and 8.55 +or- 0.76 [P <0.01] compared with 2.38 +/- 0.21 for the negative control. Mitomycin C at 1 mg/kg b. wt. [positive control] induced a much highereffect 13.36 +/- 0.78 [P <0.01]