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  1. Beh ZY, Hasan MS, Lai HY, Kassim NM, Md Zin SR, Chin KF
    BMC Anesthesiol, 2015;15:105.
    PMID: 26194896 DOI: 10.1186/s12871-015-0090-0
    The brachial plexus at the infraclavicular level runs deeper compared to its course proximally, giving rise to impaired needle visualisation due to the steep angle of needle insertion with the current ultrasound-guided approach. A new posterior parasagittal in-plane ultrasound-guided infraclavicular approach was introduced to improve needle visibility. However no further follow up study was done.
  2. Md Zin SR, Kassim NM, Mohamed Z, Fateh AH, Alshawsh MA
    J Ethnopharmacol, 2019 Dec 05;245:112180.
    PMID: 31445135 DOI: 10.1016/j.jep.2019.112180
    ETHNOPHARMACOLOGICAL RELEVANCE: Anastatica hierochuntica (A. hierochuntica) is a plant consumed in folk medicine for the treatment of reproductive system related problems and metabolic disorders. It is of concern that the herb is commonly consumed by pregnant women towards the end of pregnancy to ease the process of labour, despite the lack of studies evaluating its safety.

    AIM OF THIS STUDY: This study aimed to investigate the potential toxicity effects of A. hierochuntica in pregnant Sprague-Dawley rats and their developing foetuses.

    MATERIALS AND METHODS: Experiments were conducted in accordance to the Organisation for Economic Co-operation and Development guideline 414. Animals were randomly divided into four groups (n = 10 females per group): negative control (received the vehicle only), experimental animals received 250, 500, and 1000 mg/kg A. hierochuntica aqueous extracts (AHAE), respectively. Treatment was administered daily by oral gavage from gestational day (GD) 6-20, and caesarian section performed on GD21.

    RESULTS: There were significant reduction in the corrected maternal weight gain of dams and body weight of foetuses in the lowest and highest dose of AHAE-treated animals compared to the control. These findings were associated with the increase in anogenital distance index and multiple congenital anomalies observed in some of the offspring. On the other hand, rats treated with 500 mg/kg showed higher embryonic survival rate with absence of significant treatment-related effect.

    CONCLUSION: Findings showed that highest and lowest doses of AHAE have prenatal toxicity effects in SD rats. Therefore, AHAE is potentially harmful to the developing foetuses especially when consumed during the period of implantation and organogenesis. As for the rats treated with 500 mg/kg AHAE, there was no significant treatment-related effect. Hence, we postulate that this finding suggests that the disruption on the hormonal regulation could have been compensated by negative feedback response. The compensated effects of AHAE at 500 mg/kg and the presence of lowest observed adverse effect level (LOAEL) at 250 mg/kg has resulted in a non-monotonous dose response curve (NMDRC), which complicates the determination of the value of no-observed-adverse effect level (NOAEL).

  3. Fateh AH, Mohamed Z, Chik Z, Alsalahi A, Md Zin SR, Alshawsh MA
    Chem Biol Interact, 2019 May 01;304:28-42.
    PMID: 30807743 DOI: 10.1016/j.cbi.2019.02.016
    Verbena officinalis is widely used by women for maintaining general health and treating various gynaecological disorders during pregnancy. A case report has indicated that the consumption of V. officinalis induced an abortifacient effect. Hence, this study aimed to investigate the prenatal developmental toxicity of this plant according to OECD guideline (no. 414). A total of 50 pregnant female rats (dams) were distributed into five groups (n = 10); 500 mg/kg 1000 mg/2000 mg/kg and 3000 mg/kg of V. offcinalis extracts and the fifth group served as a normal control. All dams received their respective oral single daily treatment from the 6th to the 20th day of gestation. Maternal clinical toxicity signs, body weight and weight gain were recorded. Caesarean sections were performed on day 21 to evaluate embryo-foetal developmental toxicity. For dams, ovaries were harvested and weighed. The number of corpora lutea, implantation sites, and resorptions were recorded. No mortality was observed in dams, but their body weight gain was significantly reduced particularly in dams treated with 2000 and 3000 mg/kg V. officinalis. Asymmetrical distribution of implantation sites and embryos were observed. Embryo-fetotoxicity retardation was observed as evident by the decrease in foetal weight, head cranium, tail length, and higher incidence in the pre-and post-implantation loss. Some foetal skeleton abnormalities such as incomplete ossification of skull, sternebrae, and metatarsal bones were observed in foetuses of the 2000 and 3000 mg/kg V. officinalis-treated dams. LC/MS analysis identified the major constituents including geniposidic acid, tuberonic acid glucoside, luteolin 7, 3'-digalacturonide, iridotrial and apigenin. The glycosylated flavonoids such as apigenin and luteolin could be responsible for the reported prenatal developmental toxicity. In conclusion, the use of V. officinalis during pregnancy is not safe indicating evidence-based toxic effects on the reproductive performance of dams and dose-dependent risk potentials to the foetuses.
  4. Md Zin SR, Mohamed Z, Alshawsh MA, Wong WF, Kassim NM
    Exp Biol Med (Maywood), 2018 Feb;243(4):375-385.
    PMID: 29237294 DOI: 10.1177/1535370217748574
    Anastatica hierochuntica L. ( A. hierochuntica), a folk medicinal plant, was evaluated for mutagenic potential via in vitro and in vivo assays. The in vitro assay was conducted according to modified Ames test, while the in vivo study was performed according to Organisation for Economic Co-operation and Development guideline for mammalian erythrocyte micronucleus assay. Four groups ( n= 5 males and 5 females per group) Sprague Dawley rats were randomly chosen as the negative control, positive control (received a single intramuscular injection of cyclophosphamide 50 mg/kg), 1000 and, 2000 mg/kg A. hierochuntica aqueous extracts. All groups except the positive control were treated orally for three days. Findings of the in vitro assay showed mutagenic potential of AHAE at 0.04 and 0.2 mg/ml. However, no mutagenic effect was demonstrated in the in vivo study up to 2000 mg/kg. No significant reduction in the polychromatic and normochromatic erythrocytes ratio was noted in any of the groups. Meanwhile, high micronucleated polychromatic erythrocytes frequency was seen in cyclophosphamide-treated group only. These findings could perhaps be due to insufficient dosage of A. hierochuntica aqueous extracts to cause genetic damage on the bone marrow target cells. Further acute and chronic in vivo toxicity studies may be required to draw pertinent conclusion on the safety aspect of A. hierochuntica aqueous extracts consumption. Impact statement In this paper, we report on the mutagenicity evaluation of Anastatica hierochuntica aqueous extract. This is a significant research in view of the popularity of this herb consumption by the people across the globe despite of limited scientific evidence on its toxicity potential. This study is intended to encourage more extensive related research in order to provide sufficient evidence and guidance for determining its safe dosage.
  5. Zin SR, Omar SZ, Khan NL, Musameh NI, Das S, Kassim NM
    Clinics (Sao Paulo), 2013;68(2):253-62.
    PMID: 23525324
    OBJECTIVES: Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats.

    METHODS: Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i) a control group that received vehicle (distilled water and Tween 80); (ii) a group treated with 10 mg/kg body weight (BW) of Genistein (Gen 10); and (iii) a group treated with a higher dose of Genistein (Gen 100). The rats were treated daily for three weeks from postnatal day 22 (P22) to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study.

    RESULTS: A reduction of the mean weekly BW gain and organ weights (uteri and ovaries) were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05). These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-a in the uterine tissues of the Genistein-treated animals compared to the control animals.

    CONCLUSION: Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors.

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